vasoactive-intestinal-peptide and pancreastatin

Patterns of elevated serum peptides may reveal additional markers and permit better classification of tumors based on (secondary) peptide secretion.. Fasting peptide profiles were obtained from 31 carcinoid patients. vasoactive intestinal peptide (VIP), pancreatic polypeptide (PP), neurotensin, substance P, gastrin-releasing polypeptide (GRP), calcitonin, gastrin, and pancreastatin were measured. Peptide elevation patterns were correlated with disease sites, syndrome, and survival.. Elevations in patients were as follows: VIP 0%, PP 13%, neurotensin 10%, substance P 20%, GRP 3%, calcitonin 10%, and gastrin 3%. There were no consistent patterns of elevated peptides with regard to site or syndrome. Pancreastatin was elevated in 81% of profiles and was the only abnormal peptide in 57% of patients.. Peptide profile results do not permit improved classification, predict syndrome development, or correlate with survival. In contrast, pancreastatin is elevated in most cases and may be utilized to monitor disease progression and evaluate response to therapy.

Topics: Biomarkers, Tumor; Calcitonin; Carcinoid Tumor; Chromogranin A; Disease Progression; Female; Gastrin-Releasing Peptide; Gastrins; Humans; Male; Neurotensin; Pancreatic Hormones; Pancreatic Polypeptide; Peptides; Predictive Value of Tests; Substance P; Vasoactive Intestinal Peptide

The concentration of pituitary adenylyl cyclase-activating polypeptide [PACAP-(1-38)] in porcine adrenal glands amounted to 14 +/- 3 pmol/g tissue. PACAP immunoreactive (PACAP-IR) fibers innervated adrenal chromaffin cells (often co-localized with choline acetyltransferase). Subcapsular fibers traversed the cortex-innervating endocrine cells and blood vessels [some co-storing mainly calcitonin gene-related peptide but also vasoactive intestinal polypeptide (VIP)]. PACAP-IR fibers were demonstrated in the splanchnic nerves, whereas IR adrenal nerve cell bodies were absent. In isolated, vascularly perfused adrenal gland, splanchnic nerve stimulation (16 Hz) and capsaicin (10(-5) M) increased PACAP-(1-38) release (1.6-fold and 6-fold respectively, P = 0.02). PACAP-(1-38) dose-dependently stimulated cortisol (2 x 10(-10) M; 24-fold increase, P = 0.02) and chromogranin A fragment (2 x 10(-9) M; 15-fold increase, P = 0.05) secretion. Both were strongly inhibited by the PAC(1)/VPAC(2) receptor antagonist PACAP-(6-38) (10(-7) M). PACAP-(6-38) also inhibited splanchnic nerve (10 Hz)-induced cortisol secretion but lacked any effect on splanchnic nerve-induced pancreastatin secretion. PACAP-(1-38) (2 x 10(-10) M) decreased vascular resistance from 5.5 +/- 0.6 to 4.6 +/- 0.4 mmHg. min. ml(-1). PACAP-(6-38) had no effect on this response. We conclude that PACAP-(1-38) may play a role in splanchnic nerve-induced adrenal secretion and in afferent reflex pathways.

Topics: Adrenal Glands; Animals; Capsaicin; Chromatography, High Pressure Liquid; Chromogranin A; Dose-Response Relationship, Drug; Epinephrine; Gene Expression; Hydrocortisone; Immunohistochemistry; In Situ Hybridization; Nerve Fibers; Neuropeptides; Norepinephrine; Pancreatic Hormones; Peptide Fragments; Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Hormone; RNA, Messenger; Splanchnic Nerves; Swine; Vascular Resistance; Vasoactive Intestinal Peptide

ECL cells are numerous in the acid-producing part of the rat stomach. They are rich in histamine and pancreastatin, a chromogranin A-derived peptide, and they secrete these products in response to gastrin. We have examined how isolated ECL cells respond to a variety of neuromessengers and peptide hormones. Highly purified (85%) ECL cells were collected from rat stomach using repeated counter-flow elutriation and cultured for 48 h before experiments were conducted. The ECL cells responded to gastrin, sulphated cholecystokinin-8 and to high K+ and Ca2+ with the parallel secretion of histamine and pancreastatin. Glycine-extended gastrin was without effect. Forskolin, an activator of adenylate cyclase, induced secretion, whereas isobutylmethylxanthine, a phosphodiesterase inhibitor, raised the basal release without enhancing the gastrin-evoked stimulation. Maximum stimulation with gastrin resulted in the release of 30% of the secretory products. Numerous neuromessengers and peptide hormones were screened for their ability to stimulate secretion and to inhibit gastrin-stimulated secretion. Pituitary adenylate cyclase activating peptide (PACAP)-27 and -38 stimulated secretion of both histamine and pancreastatin with a potency greater than that of gastrin and with the same efficacy. Related peptides, such as vasoactive intestinal peptide, helodermin and helospectin, stimulated secretion with lower potency. The combination of EC100 gastrin and EC50 PACAP produced a greater response than gastrin alone. None of the other neuropeptides or peptide hormones tested stimulated secretion. Serotonin, adrenaline, noradrenaline and isoprenaline induced moderate secretion at high concentrations. Muscarinic receptor agonists did not stimulate secretion, and histamine and selective histamine receptor agonists and antagonists were without effect. This was the case also with GABA, aspartate and glutamate. Somatostatin and galanin, but none of the other agents tested, inhibited gastrin-stimulated secretion. Our results reveal that not only gastrin but also PACAP is a powerful excitant of the ECL cells, that not only somatostatin, but also galanin can suppress secretion, that muscarinic receptor agonists fail to evoke secretion, and that histamine (and pancreastatin) does not evoke autofeedback inhibition.

Topics: Animals; Calcium; Cells, Cultured; Chromogranin A; Enterochromaffin-like Cells; Gastrins; Gastrointestinal Hormones; Histamine; Histamine Release; Immunohistochemistry; Microscopy, Electron; Neuropeptides; Pancreatic Hormones; Potassium; Rats; Receptors, Cholecystokinin; Sincalide; Vasoactive Intestinal Peptide

The purpose of this study was to observe the effect of marathon running on the release of gastrointestinal hormones and whether these might be related to gastrointestinal disturbances in marathon runners. Vasoactive intestinal polypeptide, gastrin, secretin, pancreatic polypeptide, neurokinin A, pancreastatin, insulin and glucagon-like peptide 1 were measured before, immediately upon finishing and 30 min after the race. Twenty-six competitors of the 1992 Belfast Marathon volunteered for this study. They had a mean age of 37 years and a mean finishing time of 239 min. Eight of the subjects complained of gastrointestinal distress during the race. The circulating concentration of all the GI hormones measured, except insulin were significantly elevated after the race. There was no significant change in glucose levels at the finish of the race. Statistical analysis revealed no direct relationship between the large increases in hormone levels and the occurrence of GI symptoms. These results show that GI hormone concentrations are affected by marathon running. Mechanisms of release and possible roles are discussed.

Topics: Adult; Chromogranin A; Female; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Male; Middle Aged; Neurokinin A; Pancreatic Hormones; Pancreatic Polypeptide; Peptide Fragments; Physical Endurance; Protein Precursors; Running; Secretin; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) receptors were investigated in rat peritoneal macrophage membranes (RPMM) using [125I]VIP as ligand. The receptor binding was rapid, reversible, saturable, specific, and dependent on time, temperature, and membrane concentration. The Scatchard analysis of binding data was consistent with the existence of two classes of VIP binding sites with Kd values of 0.60 +/- 0.08 and 275 +/- 39 nM and binding capacities of 580 +/- 71 and 72,500 +/- 810 fmol VIP/mg protein, respectively. The interaction showed a high degree of specificity, as suggested by competitive displacement experiments with several peptides structurally or not structurally related to VIP. These pharmacological studies showed the following order of potency: VIP (IC50 = 1 nM) > rGRF (IC50 = 13 nM) > PHI (IC50 = 421 nM) >> secretin. Glucagon, somatostatin, insulin octapeptide of cholecystokinin [CCK(26-33)], and pancreastatin were ineffective at concentrations up to 1 microM. Binding of [125I]VIP to membranes is markedly reduced by increasing the ionic strength of incubation medium. Treatment of membranes with dithiothreitol, trypsin, and phospholipases A2 and C resulted in a loss of the ability of these membranes to bind VIP. However, treatment with phospholipase D did not affect binding of VIP by membranes. The molecular characterization of VIP receptors in RPMM was performed after [125I]VIP cross-linking to membranes using the cross-linker dithiobis (succinimidyl propionate). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane proteins revealed specific [125I]VIP-protein complexes of M(r) 55,000 +/- 1700, 35,000 +/- 900, and 22,000 +/- 500.

Topics: Animals; Binding, Competitive; Cell Membrane; Chromogranin A; Dithiothreitol; Insulin; Macrophages, Peritoneal; Molecular Weight; Neuropeptides; Pancreatic Hormones; Phospholipases; Protein Binding; Rats; Receptors, Vasoactive Intestinal Peptide; Salts; Trypsin; Vasoactive Intestinal Peptide

The identification of pancreastatin in pancreatic extracts prompted the investigation of its effects on islet cell function. However, in most of the investigations to date, pig pancreastatin was tested in heterologous species. Since there is great interspecies variability in the amino acid sequence of pancreastatin, we have investigated the influence of rat pancreastatin on insulin, glucagon and somatostatin secretion in a homologous animal model, namely the perfused rat pancreas. During 5.5 mM glucose infusion, pancreastatin (40 nM) inhibited insulin secretion (ca. 40%, P less than 0.025) as well as the insulin responses to 10 mM arginine (ca. 50%, P less than 0.025) and to 1 nM vasoactive intestinal polypeptide (ca. 50%; P less than 0.05). Pancreastatin failed to significantly modify glucagon or somatostatin release under any of the above experimental conditions. In addition, a lower pancreastatin concentration (15.7 nM) markedly suppressed the insulin release evoked by 11 mM glucose (ca. 85%, P less than 0.05). Our present observations reinforce the concept that pancreastatin is an effective inhibitor of insulin secretion, influencing the B-cell function directly and not through an A-cell or D-cell paracrine effect.

Topics: Animals; Arginine; Chromogranin A; Glucagon; Glucose; Insulin; Insulin Antagonists; Insulin Secretion; Male; Pancreas; Pancreatic Hormones; Perfusion; Rats; Rats, Inbred Strains; Somatostatin; Vasoactive Intestinal Peptide

Pancreastatin is a 49-amino acid straight chain molecule isolated from porcine pancreatic extracts. In the perfused rat pancreas, this peptide has been shown to inhibit unstimulated insulin release and the insulin responses to glucose, arginine, and tolbutamide. To further explore the influence of pancreastatin on islet cell secretion, the effect of synthetic porcine pancreastatin (a 2-micrograms priming dose, followed by constant infusion at a concentration of 15.7 nmol/L) was studied on the insulin, glucagon, and somatostatin responses to 1 nmol/L vasoactive intestinal peptide (VIP), 1 nmol/L gastric inhibitory peptide (GIP), and 1 nmol/L 26 to 33 octapeptide form of cholecystokinin (8-CCK). The effect of pancreastatin on the insulin and somatostatin secretion elicited by glucagon (20 nmol/L) was also examined. Pancreastatin infusion consistently reduced the insulin responses to VIP, GIP, and 8-CCK without modifying glucagon or somatostatin release. It also inhibited the insulin release but not the somatostatin output induced by glucagon. These observations broaden the spectrum of pancreastatin as an inhibitor of insulin release. The finding that pancreastatin does not alter glucagon or somatostatin secretion supports the concept that it influences the B cell directly, and not through an A cell or D cell paracrine effect.

Topics: Animals; Chromogranin A; Gastric Inhibitory Polypeptide; Glucagon; In Vitro Techniques; Insulin; Insulin Secretion; Islets of Langerhans; Kinetics; Male; Pancreatic Hormones; Perfusion; Rats; Rats, Inbred Strains; Sincalide; Vasoactive Intestinal Peptide