neuromedin-b and litorin

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

In the estrogen-treated rat myometrium, bombesin (Bn) and related agonists triggered contraction and the increased generation of inositol phosphates. The relative order of potencies was identical for both responses: Bn = gastrin releasing peptide (GRP) = litorin = neuromedin C >> neuromedin B. Two specific GRP-preferring receptor antagonists, namely [D-Phe6]Bn-(6-13) methyl ester and [Leu14,psi 13-14]Bn were inhibitory for both Bn-mediated tension and generation of inositol phosphates. [125I-Tyr4]Bn bound to myometrial membranes with high affinity (Kd = 104 pM) to a single class of sites in a saturable and reversible manner. The relative potencies for inhibiting binding were GRP = litorin = [Tyr4]Bn (Ki = 0.4 to 0.6 nM) >> neuromedin B (Ki = 10.3 nM). The high affinity displayed by [D-Phe6]Bn-(6-13) methyl ester (Ki = 2.8 nM) and [Leu14,psi 13-14]Bn (Ki = 35 nM) for competing for [Tyr4]Bn binding supported the involvement of a GRP-preferring Bn receptor. Guanine nucleotides decreased the binding of [125I-Tyr4]Bn and accelerated the rate of ligand dissociation, reflecting the coupling of receptors to guanine nucleotide regulatory proteins (G proteins). The results demonstrate that rat myometrium expresses functional GRP-preferring Bn receptors whose activation stimulates the phospholipase C pathway, pertussis toxin-insensitive event that contributes to Bn-mediated uterine contractions.

Topics: Adenosine Triphosphate; Animals; Binding, Competitive; Bombesin; Cell Membrane; Chromatography, High Pressure Liquid; Female; Gastrin-Releasing Peptide; GTP-Binding Proteins; Guanosine 5'-O-(3-Thiotriphosphate); Guanylyl Imidodiphosphate; In Vitro Techniques; Inositol Phosphates; Kinetics; Muscle, Smooth; Myometrium; Neurokinin B; Oligopeptides; Peptide Fragments; Peptides; Pertussis Toxin; Rats; Rats, Wistar; Receptors, Bombesin; Signal Transduction; Uterine Contraction; Virulence Factors, Bordetella

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