gastrin-releasing-peptide and gastrin-releasing-peptide-(14-27)

Previously, we have shown that bombesin-like peptide (BLP) promotes fetal lung development in rodents and humans but mediates postnatal lung injury in hyperoxic baboons. The present study analyzed the normal ontogeny of BLP and BLP receptors as well as the effects of BLP on cultured normal fetal baboon lungs. Transcripts encoding gastrin-releasing peptide (GRP), a pulmonary BLP, were detectable on gestational day 60 (ED60), peaked on approximately ED90, and then declined before term (ED180). Numbers of BLP-immunopositive neuroendocrine cells peaked from ED80 to ED125 and declined by ED160, preceding GRP-receptor mRNAs detected from ED125 until birth. BLP (0.1-10 nM) stimulated type II cell differentiation in organ cultures as assessed by [(3)H]choline incorporation into surfactant phospholipids, electron microscopy, and increased surfactant protein (SP) A- and/or SP-C-immunopositive cells and SP-A mRNA. BLP also induced neuroendocrine differentiation on ED60. Cell proliferation was induced by GRP, peaking on ED90. Similarly, blocking BLP degradation stimulated lung growth and maturation, which was completely reversed by a BLP-specific antagonist. The dissociation between GRP and GRP-receptor gene expression during ontogeny suggests that novel BLP receptors and/or peptides might be implicated in these responses.

Topics: Amino Acid Sequence; Amphibian Proteins; Animals; Anti-Inflammatory Agents; Antimicrobial Cationic Peptides; Cell Differentiation; Cell Division; Choline; Dexamethasone; Dipeptides; DNA Primers; Epidermal Growth Factor; Fetus; Gastrin-Releasing Peptide; Gene Expression Regulation, Developmental; In Situ Hybridization; Lung; Molecular Sequence Data; Neprilysin; Oligopeptides; Organ Culture Techniques; Papio; Peptide Fragments; Peptides; Protease Inhibitors; Proteolipids; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants; Pyrrolidonecarboxylic Acid; Receptors, Bombesin; RNA, Messenger; Tritium

Extracts of human term amnion, placenta, and chorion/decidual tissue (n = 5) contained gastrin-releasing peptide-like immunoreactivity (GRPLI) in amounts of 4.7 +/- 2.9 (pmol/g wet wt; mean +/- SEM), 3.6 +/- 1.1 and 2.9 +/- 1.5, respectively. Using C-terminally directed antisera and gel filtration chromatography and reverse-phase high-performance liquid chromatography (HPLC), each tissue contained molecular forms consistent with the presence of GRP1-27 and GRP18-27 but also contained larger amounts of two GRPLI peaks, which apparently are novel GRP-like peptides. In contrast, tissue extracts of human fetal lung contained only GRP1-27, GRP14-27, and GRP18-27. Using RT-PCR and specific GRP primers and probes, messenger RNA encoding for GRP was readily demonstrable from 6-weeks gestation throughout pregnancy to term in full-thickness membranes, placental villi, and decidua. Positive immunohistochemical staining for GRP occurred in extravillous trophoblasts in decidual septa and fetal membranes, cytotrophoblasts, syncytiotrophoblast, and certain stromal cells in placental villi and amniotic epithelium. GRPLI and GRP messenger RNA were present from the earliest dates examined (6-9 weeks) throughout pregnancy to term. Given the proven trophic nature of GRP and related peptides, these peptides may play important roles in maternal, placental, and fetal development during human pregnancy.

Topics: Amnion; Bombesin; Chorion; Chromatography, Gel; Chromatography, High Pressure Liquid; Decidua; DNA Primers; Female; Gastrin-Releasing Peptide; Humans; Immunohistochemistry; Peptide Fragments; Peptides; Placenta; Polymerase Chain Reaction; Pregnancy; Radioimmunoassay; RNA-Directed DNA Polymerase; RNA, Messenger

The effects of bombesin/gastrin-releasing peptide (BN/GRP) on c-fos and c-jun gene expression were investigated using small cell lung cancer (SCLC) cells. BN (10 nM) increased c-fos mRNA fivefold using NCI-H345 or NCI-H510 cells. The increase was concentration dependent with 1 nM BN half-maximally increasing c-fos mRNA. Also, the increase in c-fos mRNA caused by BN was time dependent, being maximal after 1 h and returning to basal values after 4 h. GRP and GRP(14-27) but not GRP(1-16) increased c-fos mRNA. BW2258U89 (1 microM), a GRP receptor antagonist, had no effect on basal c-fos but inhibited the increase in c-fos mRNA caused by 10 nM BN. Also, BN transiently increased c-jun mRNA twofold and the increase caused by BN was blocked by BW2258U89. These data suggest that GRP receptors may regulate nuclear oncogene gene expression in SCLC cells.

Topics: Bombesin; Carcinoma, Small Cell; Gastrin-Releasing Peptide; Gene Expression; Genes, fos; Genes, jun; Humans; Lung Neoplasms; Oligopeptides; Peptide Fragments; Peptides; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; RNA, Messenger; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured

The distribution of gastrin-releasing peptide (14-27)/bombesin-like immunoreactivity was studied in the brain of the teleost Oncorhynchus mykiss using an indirect immunoperoxidase technique. Cell bodies were only found in the hypothalamic nuclei posterioris periventricularis, the anterior part of the recessus lateralis, and in the recessus posterioris. Immunoreactive fibers were widely distributed in the diencephalon, midbrain, and hindbrain. The highest density of immunoreactive fibers was found in the hypothalamus, whereas a moderate to low density of fibers was visualized in the periventricular thalamus. In the midbrain, a moderate density of fibers was observed at the level of the nuclei lateralis and centralis of the torus semicircularis, the stratum album centrale of the optic tectum, the nucleus of the rostral mesencephalic tegmentum, the nuclei lateralis valvulae, the lemnisci lateralis, istmi and locus coeruleus, as well as in the hindbrain at the level of the nuclei gustatorius secundarius, cerebelli, descendens nervi trigemini, and funiculi lateralis. These data suggest that the peptide could be involved in neuroendocrine (LT, nRL, nRP), visual (OT, nRTM, TS, Is), auditory (TS), and nociceptive (Vd, nufl) mechanisms.

Topics: Animals; Bombesin; Brain Chemistry; Diencephalon; Gastrin-Releasing Peptide; Immunoenzyme Techniques; Mesencephalon; Neurons; Oncorhynchus mykiss; Peptide Fragments; Peptides; Rhombencephalon; Telencephalon

Female Syrian golden hamsters with N-nitroso-bis (2-oxopropyl) amine (BOP)-induced pancreatic cancers were treated for 2 months with bombesin/gastrin-releasing peptide (GRP) antagonist D-Tpi6,Leu13 psi(CH2NH)Leu14 bombesin(6-14) (RC-3095). Bombesin and GRP(14-27) were also administered alone and in combination with the antagonist RC-3095. RC-3095 exerted a dose-dependent inhibitory effect on growth of pancreatic cancers. The number of animals with pancreatic cancers was significantly lower in the group treated with 60 micrograms/day of RC-3095 and the weight of tumorous pancreata was reduced. Administration of bombesin or GRP alone did not stimulate the growth of pancreatic tumors and, in fact, had a slightly suppressive effect on cancers which was significant only in Experiment I. Bombesin and GRP (14-27) given together with RC-3095 did not nullify the inhibitory effect of the antagonist on pancreatic cancer growth. Actually, a greater inhibition of pancreatic tumors was observed after administration of RC-3095 together with bombesin or GRP, than with RC-3095 alone. The mechanism of action of bombesin, GRP, and bombesin antagonists on pancreatic cancers appears to be complex. The inhibitory effect of bombesin antagonists on pancreatic cancer growth was accompanied by a decrease in the binding capacity of EGF receptors in tumor membranes. Administration of bombesin also caused a down-regulation of EGF receptors and the greatest decrease in binding capacity of EGF receptors was observed after treatment with RC-3095 in combination with GRP. Inhibition of pancreatic cancer can thus be tentatively explained by some common pathways in the action of bombesin, GRP and their antagonists, that could be mediated by interference with EGF-receptor mechanisms.

Topics: Animals; Body Weight; Bombesin; Carcinoma; Cricetinae; Dose-Response Relationship, Drug; Down-Regulation; Epidermal Growth Factor; ErbB Receptors; Female; Gastrin-Releasing Peptide; Gastrins; Growth Hormone; Insulin-Like Growth Factor I; Mesocricetus; Nitrosamines; Pancreatic Neoplasms; Peptide Fragments; Peptides; Receptors, Bombesin; Receptors, Neurotransmitter

Recently synthesized highly specific and potent bombesin receptor antagonists permit study of the role of endogenous bombesin-like peptides in the physiological regulation of pancreatic secretion. We now tested the action of three novel pseudononapeptide bombesin/gastrin releasing peptide (GRP) antagonists (RC-3095, RC-3100 and RC-3120) on amylase release in vitro from isolated rat pancreatic acini and on protein secretion in vivo in chronic pancreatic fistula rats. In isolated pancreatic acini, all three bombesin receptor antagonists inhibited the amylase secretion induced by bombesin by shifting to the right the amylase response to bombesin without altering the maximal response. These antagonists alos reduced concentration dependently the near-maximal amylase response to bombesin, the concentration required for 50% reduction (IC50) being about 10(-7) M for RC-3095 and RC-3100 and 10(-6) M for RC-3120. None of the bombesin/GRP antagonists used affected the amylase response to CCK, pentagastrin or urecholine. In conscious rats with a chronic pancreatic fistula, all three bombesin antagonists shifted to the right the pancreatic protein response to graded doses of bombesin without changing the maximal response. These antagonists inhibited the protein response to constant background stimulation with bombesin in a dose-dependent manner, the ID50 being about 20 nmol/kg per h for RC-3095 and RC-3100 and about 160 nmol/kg per h for RC-3120. None of the antagonists significantly affected basal pancreatic secretion or secretion induced by sham-feeding, ordinary feeding or the diversion of pancreatic juice from the duodenum. These results indicate that exogenous bombesin is a potent direct stimulant of pancreatic enzyme secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amino Acid Sequence; Amylases; Animals; Bombesin; Gastrin-Releasing Peptide; In Vitro Techniques; Molecular Sequence Data; Pancreas; Peptide Fragments; Peptides; Rats; Receptors, Bombesin; Receptors, Neurotransmitter

Four new and specific pseudononapeptide bombesin/gastrin-releasing peptide (GRP) receptor antagonists, containing the D-forms of Trp or Trp analogue (Tpi) at position 6, were studied for their effects on the endocrine pancreas and GRP-(14-27)-induced gastrin release in pentobarbital-anesthetized rats. One of the analogues, D-Tpi6,Leu13-psi (CH2NH)Leu14-bombesin-(6-14) (RC-3095), was injected into the lateral brain ventricle just preceding intracerebroventricular administration of GRP-(14-27) to evaluate its antagonistic effect on GRP-induced serum growth hormone (GH) suppression. Analogues RC-3095, D-Trp6,Leu13-psi (CH2NH)Leu14-bombesin-(6-14) (RC-3125), and D-Trp6,Leu13-psi (CH2NH)Phe14-bombesin-(6-14) (RC-3420), but not D-Tpi6,Leu13-psi (CH2NH)Phe14-bombesin-(6-14) (RC-3105), significantly (P < 0.01) inhibited GRP-(14-27)-stimulated serum gastrin secretion. Analogues RC-3095, RC-3420, and RC-3105, but not RC-3125, demonstrated significant (P < 0.05) antagonistic activities on GRP-(14-27)-stimulated plasma glucagon secretion. Intracerebroventricular injection of RC-3095 (10 micrograms) immediately before GRP-(14-27) (1 microgram) completely prevented the GRP-(14-27)-induced serum GH suppression. These results indicate that 1) marked differences exist in the ability of these analogues to antagonize GRP-(14-27)-induced gastrin or glucagon release, suggesting the existence of different bombesin/GRP receptor subtypes, and 2) the central effect of bombesin/GRP on GH release from the pituitary is probably mediated through specific bombesin/GRP receptors.

Topics: Amino Acid Sequence; Animals; Blood Glucose; Bombesin; Endocrine Glands; Gastrin-Releasing Peptide; Gastrins; Glucagon; Growth Hormone; Insulin; Male; Molecular Sequence Data; Peptide Fragments; Peptides; Rats; Rats, Sprague-Dawley

This study was performed to evaluate the efficacy and duration of action of a new bombesin antagonist D-Tpi6,Leu13 psi (CH2NH)Leu14-bombesin (6-14) (RC-3095), given by different routes of administration, in suppressing gastrin releasing-peptide (GRP(14-27))-stimulated gastrin release in rats. First, we showed that GRP(14-27) itself was highly active when administered by different routes. GRP(14-27), given to rats at a dose of 25 micrograms/100 g b.w. significantly increased serum gastrin levels 3 and 6 min after intravenous and for more than 30 min after subcutaneous administration or pulmonary inhalation. RC-3095 was then injected subcutaneously, intravenously and also delivered by pulmonary inhalation at a dose of 10 micrograms/100 g b.w. in each case to seven male rats 2, 30, 60 or 120 min prior to i.v. administration of 5 micrograms GRP(14-27). RC-3095 administered 2 min prior to GRP(14-27) decreased the gastrin response to GRP(14-27), measured as area under the curve, by 81% in the intravenously injected group and 64% in the pulmonary inhalation group in the first 6 min. When GRP(14-27), was given 30 min after administration of RC-3095, the gastrin response was decreased by 52% in the subcutaneous group, 49% in the pulmonary inhalation group and 11% in the intravenous group during the first 6 min. RC-3095 delivered subcutaneously or by pulmonary inhalation 1 h before GRP(14-27) was also able to significantly inhibit gastrin release. Analysis of the data revealed that the bioavailability of RC-3095 given by the pulmonary inhalation route was about 69% of the s.c. route.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Animals; Bombesin; Gastrin-Releasing Peptide; Gastrins; Injections, Intravenous; Injections, Subcutaneous; Male; Peptide Fragments; Peptides; Radioimmunoassay; Rats; Rats, Sprague-Dawley

Immunoreactivity related to the gastrin-releasing peptide (GRP) precursor was detected in four different human breast cancer cell lines. The amounts and the characteristics in extracts from different breast carcinoma cells were compared with cell extracts from small cell lung cancer (SCLC) cells. Two different radioimmunoassays were employed, directed against the amino acid sequence 14-27 of GRP (IR-GRP) or the 42-53 amino acid sequence at the C-terminal end of the GRP precursor (GRP precursor fragment). In extracts from T47D cells cultured under serum free conditions, IR-GRP coeluted with GRP(14-27) or GRP(18-27) in Sephadex G-50 chromatography. No immunoreactivity was detected in the fractions containing high molecular weight components. In a total of 41 human breast carcinoma biopsies from different postmenopausal patients, IR-GRP was detected by immunohistological staining in 39% of the samples. When the GRP(14-27) peptide was added exogenously to breast cancer and SCLC cell lines under serum-free culture conditions, (3H)-thymidine incorporation was stimulated by GRP(14-27) in the SCLC cell lines. Of the breast cancer cell lines only the T47D cell line responded with an increase in (3H)-thymidine incorporation comparable to the increase observed with SCLC cells. Recently, it has been reported that GRP-like receptors are present in some human breast cancer cell lines, including the T47D cell line studied here. The breast cancer cell line T47D therefore expresses the GRP peptide and the receptor for GRP. The identification of GRP-like receptors on T47D cells is in accordance with our present observation of a growth response to GRP(14-27) as evaluated by increased (3H)-thymidine incorporation.

Topics: Breast Neoplasms; Carcinoma, Small Cell; Cell Division; Gastrin-Releasing Peptide; Humans; Lung Neoplasms; Peptide Fragments; Peptides; Protein Precursors

A preliminary morphological study on human fetal lungs with positive maternal smoking history demonstrated alterations of the neuroepithelial bodies (NEBs). We studied human fetal lung tissue between the gestational ages of 12 weeks and 19 weeks, comprising 12 cases with a smoking history during pregnancy (Group 1) and eight cases without a smoking history during pregnancy (Group 2). We demonstrated, by immunocytochemistry, the presence of gastrin-releasing peptide (GRP) gene products: GRP 14-27 in all 20 cases, and C terminal peptide of pro-GRP (C-flanking peptide) in 17 cases. Quantification of the neuroepithelial cells (NECs) was made by computer-enhanced image analysis using the Context Vision system, expressing 1) the total stained areas of the NECs per unit area of section and 2) the total staining areas of the NECs per unit area of airway epithelium, measured as the area of cytokeratin immunoreactivity in an adjacent section. The results show no statistically significant difference between groups 1 and 2 for either GRP 14-27 or C-flanking peptides. The apparent lack of influence of maternal smoking during pregnancy on the expression of GRP gene products in the NECs could be a reflection of inherently reduced reactivity of the cells during the gestation period studied. However, a larger series is needed before any conclusions can be made. Alternatively, the adverse effects of smoking might be reflected during the canalicular phase of lung development; an increased immunoreactivity appears to be present during that period. The expression of pro-GRP gene products in the pulmonary NECs of older fetuses and neonates with maternal smoking history during pregnancy requires further study.

Topics: Female; Fetus; Gastrin-Releasing Peptide; Humans; Immunohistochemistry; Keratins; Lung; Peptide Fragments; Peptides; Pregnancy; Smoking

The production and postsecretory stability of gastrin-releasing peptide (GRP) and the C-terminal part of the GRP precursor were studied in small cell lung cancer cell lines using RIAs developed against these two parts of the precursor. In three otherwise different cell lines (NIC-H345, NIC-H69, and NIC-H510), similar chromatographic patterns of mainly GRP-(18-27) and some GRP-(14-27) along with large fragments of the C-terminal counterpart of the precursor were found to be stored in the cells. In tissue culture medium, gel filtration chromatography indicated that postsecretory limited proteolysis of the GRP precursor fragments occurred. The amount of accumulated immunoreactivity varied among the three cell lines and between the two parts of the precursor. In medium in which only low amounts of GRP immunoreactivity accumulated, the radiolabeled GRP was degraded rapidly. When incubated with plasma, GRP-(14-27) disappeared within a few hours, whereas the C-terminal precursor fragments were stable. It is concluded that the postsecretory stability of peptides excised from the GRP precursor in small cell lung cancer cells varies under tissue culture conditions, but epitopes in the C-terminal part of the precursor are more stable in plasma than the small GRP peptides and, thus, may serve as a better indicator than GRP itself for expression of the GRP precursor in cancer cells.

Topics: Amino Acid Sequence; Biomarkers, Tumor; Bombesin; Carcinoma, Small Cell; Cell Line; Chromatography, Gel; Chromatography, High Pressure Liquid; Chromosome Mapping; Gastrin-Releasing Peptide; Gene Expression; Humans; Immunoradiometric Assay; In Vitro Techniques; Lung Neoplasms; Molecular Sequence Data; Peptide Fragments; Peptides; Sequence Homology, Nucleic Acid; Substance P

The present study examined and compared the effects of muscarinic blockade, beta-adrenergic blockade and immunoneutralization of the neuropeptide gastrin-releasing peptide (GRP) on distention-induced gastric acid secretion and gastrin release. In response to distention of rat stomachs with 0.9% NaCl, acid output rose from 3.5 +/- 0.5 mumol H+/30 min to 15.4 +/- 2.5 mumol H+/30 min (P less than 0.01). Intravenous administration of 4 mg/kg propranolol did not affect the acid secretory response to distention, however both 2 mg/kg atropine and 6 mg/kg pirenzepine significantly decreased gastric acid secretion by 44.8 +/- 7.8% and 40.9 +/- 5.7% (P less than 0.05), respectively. When specific antibodies to GRP were infused intravenously, the acid secretory response to distention was nearly abolished, decreasing to 5.1 +/- 0.8 mumol H+/30 min (P less than 0.01). In contrast to the effects on acid secretion, GRP antiserum did not significantly alter the gastrin release observed following distention. Results of these studies indicate that, under the conditions of these experiments, the acid secretory response to gastric distention may be independent of its effect on gastrin release. Although distention-induced gastric acid secretion may be partially governed by muscarinic pathways, the acid secretory response to distention in the rat appears to involve GRP-containing neurons.

Topics: Animals; Antibodies; Bombesin; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Male; Neuropeptides; Peptide Fragments; Peptides; Radioimmunoassay; Rats; Rats, Inbred Strains

Purified adult rat Leydig cells were found to produce gastrin-releasing peptide (GRP) by radioimmunoassay (RIA). Gel chromatography of the extracted material showed a single peak of GRP immunoreactivity. Further high pressure liquid chromatography (HPLC) analysis resolved the extract into two peaks that closely resembled the C-terminal fragment of GRP, GRP18-27 and GRP14-27. Immunohistochemical studies revealed specific staining for GRP in the Leydig cells of adult rat testis. These results demonstrate, by a number of independent criteria, that rat Leydig cells contain substances which behave like authentic GRP-like peptides. Since the peptides appear to be of local origin, a paracrine function within the rat testis is suggested.

Topics: Animals; Bombesin; Chromatography, Gel; Chromatography, High Pressure Liquid; Gastrin-Releasing Peptide; Immunoenzyme Techniques; Leydig Cells; Male; Peptide Fragments; Peptides; Radioimmunoassay; Rats; Rats, Inbred Strains

A selected group of 263 pulmonary neuroendocrine tumours comprised 156 small cell carcinomas, five combined cell carcinomas, nine atypical carcinoid/small cell carcinomas, 32 atypical carcinoids, ten large cell/small cell carcinomas, and 51 carcinoid tumours. These were compared with a group of 109 non-small cell carcinomas, using four markers of neuroendocrine differentiation to determine differences in reactivity between the two groups and among the variants of neuroendocrine tumour. The antibodies used were neuron-specific enolase (NSE), protein gene product (PGP) 9.5, human bombesin, and the C-terminal flanking peptide of human bombesin (CTP). Most small cell carcinomas, carcinoid tumours, and atypical carcinoid variants showed immunoreactivity for both NSE and PGP 9.5 but a significant number of non-small cell carcinomas, mainly squamous cell carcinomas, were also positive (11 and 35 per cent, respectively). Bombesin was specific for neuroendocrine tumours, being demonstrable in 35 per cent carcinoids and 24 per cent small cell carcinomas, but staining was focal and often confined to scattered cells. Diffuse strongly positive immunoreactivity for CTP was seen in the majority of malignant neuroendocrine tumours, but only 12 per cent of carcinoid tumours were positive and non-small cell carcinomas were negative. CTP is therefore of potential value as a specific marker of malignant neuroendocrine tumours, particularly if the amount of biopsy material is limited and the tumour is an unusual variant, such as atypical carcinoid or large cell-small cell carcinoma.

Topics: Biomarkers, Tumor; Bombesin; Carcinoid Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Gastrin-Releasing Peptide; Humans; Immunoenzyme Techniques; Lung Neoplasms; Neuropeptides; Peptide Fragments; Peptides; Phosphopyruvate Hydratase; Ubiquitin Thiolesterase

In order to examine hepatic clearance of gastrointestinal regulatory peptides, rat livers were perfused in situ, and radiolabelled somatostatin (S-14, S-28), gastrin-releasing peptide (GRP-14, GRP-27), and vasoactive intestinal peptide (VIP) were injected into the portal vein and hepatic venous effluent was collected. S-14 and S-28 were not affected significantly by hepatic transit: 91.6 +/- 2.8% (SEM) of S-14 and 95.9 +/- 2.2% of S-28 were recovered, and neither peptide was degraded by hepatic transit, as determined by immunoprecipitation and gel chromatography. GRP-14 and GRP-27 were also not affected by hepatic transit: 91.5 +/- 1.6% of GRP-14 and 94.4 +/- 2.4% of GRP-27 were recovered intact. In contrast, when radiolabelled VIP was infused into the portal vein, 56.7 +/- 7.4% of injected labelled VIP appeared in the hepatic venous effluent, of which only 33.5 +/- 1.2% was intact peptide. Results of these studies indicate that enteric VIP released into the splanchnic/portal circulation is cleared by hepatic transit. However, somatostatin and GRP peptides appear to traverse the liver intact and could potentially produce systemic biological effects.

Topics: Animals; Gastrin-Releasing Peptide; Gastrointestinal Hormones; Liver; Male; Peptide Fragments; Peptides; Rats; Rats, Inbred Strains; Somatostatin; Somatostatin-28; Vasoactive Intestinal Peptide

A differential biological potency of bombesin (BBS), compared with its mammalian counterpart gastrin-releasing peptide (GRP), has been reported in several biological systems in rodents. In the present study we have examined the relative potency of BBS, GRP-(1-27) (GRP-L), and GRP-(14-27) (GRP-S) on the release of gastrin and somatostatin (SRIF) from the isolated perfused rat stomachs. Male rats were fasted overnight and the stomachs perfused via the celiac artery. Increasing doses of BBS, GRP-L, and GRP-S were perfused for 15 min each and the effluent collected for measurement of gastrin and SRIF. The release of gastrin and SRIF in response to the GRP analogues was biphasic, with a peak increase occurring within the first 5 min, followed by a sustained increased secretion. The release of gastrin in response to 10(-10)-10(-9) M concentrations of the peptides was strongest with GRP-S (1.5-2.0 times higher than that released by BBS and GRP-L), although at higher concentrations (10(-8) M), the response to all three analogues was similar. The release of SRIF, on the other hand, was significantly higher in the presence of BBS compared with that in response to GRP-S, while GRP-L was ineffective. These studies indicate that the biological potency of BBS compared with its mammalian counterpart, GRP, is different on the two cell populations [gastrin (G) and SRIF (D)].

Topics: Animals; Bombesin; Dose-Response Relationship, Drug; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; In Vitro Techniques; Male; Peptide Fragments; Peptides; Rats; Somatostatin

Gastrin-releasing peptide and the carboxyterminal fragments gastrin-releasing peptide [14-27] and [18-27] are found by radioimmunology and high performance liquid chromatography to be present in heat-inactivated fetal calf sera. Peptides containing the carboxyterminal sequence of gastrin-releasing peptide are known to display mitogenic activity. Thus, gastrin-releasing peptide represents a new class of mitogenic factors that are present in heat-inactivated fetal calf serum.

Topics: Animals; Blood; Cattle; Chromatography, High Pressure Liquid; Culture Media; Fetus; Gastrin-Releasing Peptide; Hot Temperature; Peptide Fragments; Peptides; Radioimmunoassay

The synthetic mammalian bombesin-like peptides, canine gastrin releasing peptide 27, 23 and 10, and porcine gastrin releasing peptide 27 were compared with amphibian bombesin 14 and 10 during intravenous infusions into six conscious dogs with chronic gastric cannulae. Gastrin and gastrin releasing peptide were measured in peripherally sampled venous blood by radioimmunoassay and gastric acid secretions were collected. All forms of gastrin releasing peptide stimulated gastrin release and gastric acid secretion in a dose-dependent manner. The larger canine and porcine peptides were more potent than the decapeptide. Bombesin 14 was more potent than bombesin 10. A rise in the venous concentration of immunoreactive gastrin releasing peptide of only 20 fmol ml-1 stimulated gastrin release to about 50% of maximal. Gastrin releasing peptide 10 was cleared from the circulation three times faster than the larger forms and this may account for the apparent differences in potency.

Topics: Animals; Bombesin; Dogs; Dose-Response Relationship, Drug; Female; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Male; Metabolic Clearance Rate; Peptide Fragments; Peptides; Stimulation, Chemical; Swine

The remission of Cushing's syndrome following surgical removal of a tumour containing bombesin-like immunoreactivity (BLI), but insignificant levels of ACTH, is described. However, an acid extract of the tumour tissue caused the release of ACTH from isolated rat anterior pituitary cells in vitro. These observations led to an investigation of the effects of synthetic C-terminal gastrin-releasing peptide (GRP(14-27] on ACTH release from isolated rat anterior pituitary cells. GRP(14-27) (10-1000 ng/ml) directly stimulated the release of ACTH in vitro, whereas lower doses (10-1000 pg/ml), ineffective themselves in eliciting ACTH release, potentiated the CRF-mediated in-vitro release of ACTH.

Topics: ACTH Syndrome, Ectopic; Adrenocorticotropic Hormone; Adult; Animals; Corticotropin-Releasing Hormone; Drug Synergism; Gastrin-Releasing Peptide; Humans; In Vitro Techniques; Male; Peptide Fragments; Peptides; Pituitary Gland, Anterior; Rats; Thyroid Neoplasms; Tissue Extracts

Bombesin and the C-terminal portion of gastrin-releasing peptide (GRP14-27) each increase clonal growth rate and colony-forming efficiency of normal human bronchial epithelial cells. These effects occur in the presence or absence of an optimal concentration (5 ng/ml) of epidermal growth factor (EGF). In contrast to EGF bombesin and GRP14-27 do not stimulate cell migration. Thus, bombesin and the C-terminal fragment of gastrin-releasing peptide represent a new class of peptides mitogenic for normal human epithelial cells.

Topics: Adult; Bombesin; Bronchi; Cell Division; Cells, Cultured; Clone Cells; Epithelium; Gastrin-Releasing Peptide; Growth Substances; Humans; Kinetics; Peptide Fragments; Peptides