neuromedin-b and ranatensin

The mammalian bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB), are structurally related neuropeptides that elicit a wide spectrum of biological activities including regulation of smooth muscle contraction, stimulation of secretion, modulation of neural activity, and growth regulation. Earlier studies have shown that GRP and NMB are expressed in different regions of both the CNS and peripheral organs. Recent ligand-binding and molecular-cloning studies have revealed two pharmacologically distinct G-protein-coupled receptor subtypes for mammalian bombesin-like peptides that have different relative affinities for GRP, NMB and bombesin receptor antagonists. Similar to the peptide ligands, the two receptor subtypes are expressed in a distinct but overlapping set of CNS regions, some of which have been identified in functional studies as sites where bombesin peptides elicit defined biological responses. Delineation of these peptide ligands and receptor subtypes will be important in future studies that explore the molecular basis for the heterogeneous nature of the responses to bombesin observed in mammalian systems.

Topics: Amino Acid Sequence; Animals; Bombesin; Brain Chemistry; Brain Mapping; Cloning, Molecular; DNA; Gastrin-Releasing Peptide; Mice; Molecular Sequence Data; Neurokinin B; Oligopeptides; Peptides; Protein Binding; Pyrrolidonecarboxylic Acid; Rats; Receptors, Bombesin; Receptors, Neurotransmitter; Sequence Homology, Nucleic Acid

Topics: Amino Acid Sequence; Animals; Bombesin; DNA; Gastrin-Releasing Peptide; Genes; Humans; Molecular Sequence Data; Neurokinin B; Oligopeptides; Peptides; Pyrrolidonecarboxylic Acid; Rana pipiens; Sequence Homology, Nucleic Acid

Neuromedin B (NMB) and neuromedin C (NMC) are peptides found in the mammalian central nervous system, and their concentrations are particularly high in the hypothalamus. The amino acid sequences of these peptides are similar to that of bombesin, which is known to induce marked hypothermia not only in amphibians but also in mammals. The effect of neuromedins and related peptides on the body temperature regulation was examined in the rat under a thermoneutral environment. The findings indicated that NMC caused moderate hypothermia following intracerebroventricular administration, while the effect of NMB was meager, suggesting that these two neuropeptides possess different physiological functions in the brain.

Topics: Amino Acid Sequence; Animals; Body Temperature; Bombesin; Brain; Injections, Intraventricular; Male; Molecular Sequence Data; Neurokinin B; Oligopeptides; Peptide Fragments; Pyrrolidonecarboxylic Acid; Rats; Rats, Wistar

The effects of bombesin, gastrin-releasing peptide, neuromedin C, ranatensin, and neuromedin B on hypothalamic arcuate neurons were tested in this study using extracellular single-unit recording in fresh brain tissue slices. Adult ovariectomized Sprague-Dawley rats were used for preparation of brain slices. All bombesin-like peptides in pmol ranges exhibited potent stimulatory effects on the firing of arcuate neurons, i.e., gastrin-releasing peptide stimulated 90.9% (n = 22), bombesin 78.0% (n = 41), neuromedin C 63.2% (n = 19), ranatensin 58.0% (n = 22), and neuromedin B 50.0% (n = 6) of arcuate neurons tested. Pretreatments with either [Leu13-psi(CH2NH)-Leu14]-bombesin or [D-Phe6,Des-Met14]-bombesin6-14 ethylamide, two bombesin antagonists, significantly blocked most of the actions of bombesin-like peptides tested. The present results further support the notion that bombesin-like peptides may play a significant role in the arcuate nucleus.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Bombesin; Female; Follow-Up Studies; Gastrin-Releasing Peptide; In Vitro Techniques; Neurokinin B; Neurons; Oligopeptides; Peptide Fragments; Peptides; Pyrrolidonecarboxylic Acid; Rats; Rats, Sprague-Dawley; Stimulation, Chemical

The effect of the bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin-C (NMC), and the ranatensin-like peptides, neuromedin-B (NMB), neuromedin-B30 (NMB30), and neuromedin-B32 (NMB32), on pituitary GH and PRL release was studied in perifused anterior pituitary aggregate cell cultures from 9- to 12-week-old male rats cultured in serum-free defined medium supplemented with 0.05 nM T3 and 4 nM dexamethasone (DEX). All peptides stimulated PRL and GH release. GRP and NMC stimulated hormone release in a concentration-dependent manner between 0.1-10 nM. NMB was slightly more potent than NMB30 and NMB32, but was significantly less potent than GRP and NMC. The magnitude of the PRL response to GRP and NMC inversely correlated with that of the GH response. Cultures with relatively low PRL response levels displayed high GH responses, whereas the opposite was found in cultures with high PRL response levels. The stimulatory actions of GRP, NMC, and NMB were blocked by the bombesin receptor antagonist Leu13 psi (CH2NH) Leu14-bombesin, supporting the specificity of the findings. Addition of 1 nM estradiol (E2) to the culture medium provoked an impressive (4- to 10-fold) increase in the magnitude of the GH response to NMC without changing the EC50 value (0.5 nM). In contrast, E2 significantly decreased the stimulation of GH release by rat GH-releasing factor. In the E2-treated aggregates 3 nM NMC stimulated GH release to a comparable extent as 0.1 nM GRF. 5 alpha-Dihydrotesterone (10 and 100 nM) and DEX (80 nM) also enhanced the GH response to NMC, but to a much smaller extent than E2. E2 had also a stimulatory effect on the PRL response to NMC, particularly in cultures with a low intrinsic PRL response. The PRL response to NMC was decreased by DEX and slightly augmented by 5 alpha-dihydrotestosterone. It is concluded that bombesin- and ranatensin-like peptides have a stimulatory effect on GH and PRL release at the pituitary level. Since their action on GH release is strongly potentiated by E2 and much less so by glucocorticoids, these peptides clearly distinguish their activity and specificity from that of the protagonist releasing factor GH-releasing factor, suggesting a role in sex-related differences in GH release or in the control of GH secretion during sexual maturation.

Topics: Animals; Bombesin; Cells, Cultured; Dexamethasone; Dihydrotestosterone; Drug Synergism; Estradiol; Gastrin-Releasing Peptide; Growth Hormone; Male; Neurokinin B; Oligopeptides; Peptide Fragments; Peptides; Pituitary Gland, Anterior; Prolactin; Pyrrolidonecarboxylic Acid; Rats; Rats, Inbred Strains

The amidated decapeptide neuromedin B (NMB) is the mammalian homolog of the amphibian bombesin-like peptide ranatensin. cDNAs encoding human neuromedin B and amphibian ranatensin were isolated from human hypothalamic and Rana pipiens skin libraries, respectively. Sequence analysis revealed that NMB is encoded in a 76-amino acid precursor and ranatensin in an 82-amino acid precursor. In the NMB preprohormone, the sequence of the large form of NMB (NMB-22) immediately follows the signal peptide and is, in turn, followed by a dibasic cleavage site and a 17-amino acid carboxyl-terminal extension peptide. The structure for the ranatensin preprohormone is very similar. RNA blot analysis shows two NMB mRNA species, each approximately 800 bases, with wide distribution in brain and gastrointestinal tract. Genomic DNA blot analysis is consistent with a single human NMB gene. Analysis of mouse-human somatic cell hybrids indicates that this gene is localized on the long arm of human chromosome 15. Since the gene for human gastrin-releasing peptide is on chromosome 18, this analysis demonstrates that the bombesin-like peptide genes are not clustered.

Topics: Amino Acid Sequence; Animals; Base Sequence; Cloning, Molecular; DNA; Mice; Molecular Sequence Data; Neurokinin B; Neuropeptides; Oligopeptides; Pyrrolidonecarboxylic Acid; Rana pipiens; RNA

The amphibian skin tetrapeptide bombesin shows potent action in reducing gastric acid secretion by intracerebral ventricular (ICV) administration in rats. In order to establish a relationship between this action and the amino acid composition of the bombesin-like peptides, most of the natural bombesin-like peptides and some synthetic analogues were tested on their ability to reduce gastric acid secretion by ICV administration. The amphibian peptides bombesin, its [Tyr4]-bombesin analogue, alytesin, ranatensin and litorin, and the mammalian peptide GRP significantly reduced gastric acid output 2 hr after peptide administration (p less than 0.01). The data support the following prerequisites for the maximal neuromodulatory role of bombesin-like peptides on gastric secretion: Trp is required at position 8; Gln and His are important at positions 7 and 12, respectively; Leu replacement by Phe, which occurs in the litorin subfamily, modifies the response; and unspecified amino acids or sequences are also involved in the N-terminal region of bombesin-like peptides. Synthetic analogues are currently being tested to confirm and extend these conclusions.

Topics: Amino Acid Sequence; Animals; Bombesin; Gastric Juice; Gastrin-Releasing Peptide; Hydrogen-Ion Concentration; Male; Neurokinin B; Oligopeptides; Peptide Fragments; Peptides; Pyrrolidonecarboxylic Acid; Rats; Secretory Rate