litorin and ranatensin

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

To examine the biochemical basis for growth factor-induced responses in human lung cancer cells, we used the quin2 technique to study the effect of the amphibian peptide bombesin and its congeners including mammalian gastrin-releasing peptide (GRP) on the intracellular free calcium level [Ca2+]i in small cell lung cancer cell lines. In five of eleven cell lines tested, Tyr4-bombesin or GRP elicited a rapid and transient increase in [Ca2+]i. The response was seen with as little as 1 nM ligand, was not affected by membrane depolarization, and derived in part from internal calcium stores. Desensitization to a second addition of active bombesin congeners occurs subsequent to initial addition of Tyr4-bombesin. Structure-activity analysis showed the carboxyl-terminal octapeptide was the active portion of the peptide. Analogs in which the carboxyl terminus was oxidized or deamidated were inactive. Ranatensin, litorin, alytesin, and GRP, but not physalaemin, were as active as Tyr4-bombesin. A monoclonal antibody to the carboxyl terminus of bombesin selectively blocked the increased [Ca2+]i elicited by Tyr4-bombesin. These studies suggest that bombesin congeners can act on some small cell lung cancer cell lines by a pathway utilizing increased [Ca2+]i.

Topics: Amino Acid Sequence; Bombesin; Calcium; Carcinoma, Small Cell; Cell Line; Dose-Response Relationship, Drug; Gastrin-Releasing Peptide; Humans; Kinetics; Lung Neoplasms; Oligopeptides; Peptides; Pyrrolidonecarboxylic Acid; Structure-Activity Relationship

Nonmammalian peptides of the tachykinin, bombesin and opioid families, injected into the brain ventricles, potently and specifically affect drinking behaviour of rats and pigeons. These peptides, or at least their counterparts, have been found in the brain of mammals and birds. It has been hypothesized that these endogenous brain peptides belong to a "brain peptidergic system" which participates in the control of water intake and body fluid homeostasis.

Topics: Angiotensin II; Animals; Bombesin; Columbidae; Drinking Behavior; Eledoisin; Endorphins; Enkephalins; Nerve Tissue Proteins; Oligopeptides; Opioid Peptides; Physalaemin; Pyrrolidonecarboxylic Acid; Rats; Substance P; Tachykinins; Vasopressins; Water-Electrolyte Balance

When dispersed acini from mouse pancreas are first incubated with bombesin, washed, and then reincubated with fresh incubation solution containing no bombesin, there is significant residual stimulation of amylase release. Induction of residual stimulation is relatively rapid in that significant stimulation occurs as early as after 15 s of first incubation with bombesin. Induction of residual stimulation of amylase release per se is temperature independent, but induction does occur more rapidly when acini are first incubated at 37 degrees C than when they are first incubated at 4 degrees C. Residual stimulation of amylase release persists for at least 75 min in acini that have been first incubated with bombesin at 37 degrees C. The maximal residual stimulation of amylase release obtained with pancreatic acini that have been first incubated with bombesin and then washed is 45% greater than the maximal stimulation obtained when bombesin is added directly to the incubation medium. In terms of their abilities to cause residual stimulation of amylase release, litorin and ranatensin are equal to bombesin in potency and efficacy. Gastrin-releasing peptide is approximately 70% as efficacious as bombesin in causing residual stimulation of amylase release.

Topics: Amylases; Animals; Bombesin; Dose-Response Relationship, Drug; Gastrin-Releasing Peptide; Male; Mice; Mice, Inbred Strains; Oligopeptides; Pancreas; Peptides; Pyrrolidonecarboxylic Acid; Stimulation, Chemical; Time Factors

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

Four dogs with chronic gastric fistulas were give intravenous bombesin nonapeptide (B9), ranatensin, and litorin by constant infusion for 90 min at 1.2 micrograms x kg-1 on separate days. A dose response study with substance P (1.5, 3.0, 60, 18 and 54 micrograms x kg-1 x h-1) was also carried out and all tests compared to a standard protein meal (10g x kg-1). Plasma gastrin and PP were measured by radioimmunoassay and gastric acid by autobiuret titration. Substance P failed to stimulate gastric acid secretion or release either pancreatic polypeptide (PP) or gastrin. Basal gastrin levels were 8 +/-2 fmol/ml. The peak increment of gastrin released by bombesin was 95 +/- 16, ranatensin 22 +/- 6, litorin 18 +/- 4, and meal 39 +/- 5 fmol/ml. Bombesin caused significantly greater release of gastrin than a meal, litorin or ranatensin (P less than 0.01). Basal gastric secretion was 23 +/- 4 microequiv./min. B9 produced a peak acid secretion of 356 +/- 124 muequiv./min. There was no significant difference between the bombesin-like peptides (P less than 0.01). Basal plasma PP was 38 +/- 12 fmol/ml. B9 produced a peak PP increment of 600 +/- 50, litorin 137 +/- 36, ranatensin 98 +/- 11, and a meal 305 +/- 58 fmol/ml. B9 released significantly more PP than either litorin of ranatensin (P less than 0.01). The different amino acid sequences of the peptides are probably responsible for their potency. The substitution of a penultimate phenylalanine residue in litorin and ranatensin for leucine in bombesin does not prevent PP or gastrin release by bombesin-like peptides. Since bombesin-like peptides are widely distributed in the gastrointestinal tract of man and stimulate both acid and gut hormone secretion, it is possible that they might play a physiological role in the modulation of gastrointestinal function.

Topics: Animals; Bombesin; Dogs; Food; Gastric Acid; Gastrins; Kinetics; Oligopeptides; Pancreatic Polypeptide; Peptide Fragments; Peptides; Pyrrolidonecarboxylic Acid; Substance P

Incubating dispersed acini from guinea pig pancreas with bombesin and then washing the cells to remove bombesin reduced the subsequent stimulation of amylase secretion caused by bombesin, litorin, or ranatensin by as much as 80%, but did not alter the stimulation of amylase secretion caused by cholecystokinin, carbamylcholine, A23187 or vasoactive intestinal peptide. This bombesin-induced desensitization was reversible, and the onset of the process, as well as its reversal, were time and temperature dependent. Neither desensitization or resensitization were inhibited by abolishing protein synthesis. The concentrations of bombesin required to cause desensitization were in the same range as those required to stimulate amylase secretion. Incubating pancreatic acini with vasoactive intestinal peptide did not reduce the subsequent stimulation of amylase secretion caused by vasoactive intestinal peptide, bombesin, or cholecystokinin. These results indicate that bombesin-induced desensitization of pancreatic acini reflects changes that occur at or close to the bombesin receptor.

Topics: Amylases; Animals; Bombesin; Calcimycin; Carbachol; Cholecystokinin; Dose-Response Relationship, Drug; Guinea Pigs; Male; Oligopeptides; Pancreas; Peptides; Pyrrolidonecarboxylic Acid; Vasoactive Intestinal Peptide