High potency of bombesin for stimulation of human gastrin release and gastric acid secretion

doi:10.1016/0167-0115(81)90052-5

Regulatory Peptides

Volume 1, Issue 4, January 1981, Pages 289-296

https://doi.org/10.1016/0167-0115(81)90052-5 Get rights and content

Abstract

Dose-response studies were performed in 6 human volunteer subjects to determine the threshold and optimal doses of intravenous bombesin for stimulation of gastric acid secretion and gastrin release. A significant stimulation of both acid and gastrin was obtained with a very low dose, 3 pmol · kg⁻¹ · h⁻¹. Peak stimulation of acid secretion (67% of pentagastrin PAO) was obtained at 12.5 pmol · kg⁻¹ · h⁻¹. Serum gastrin response to this dose of bombesinn was similar to that obtained after a high protein meal. Higher doses of bombesin caused further increases in serum gastrin but not in acid secretion. Since very low doses of bombesin, too small to produce detectable increases in immunoreactive serum bombesim, caused parallel increases in gastrin and acid secretion, it is possible that the bombesin-like peptides present in human gastrointestinal tissues contribute to regulation of human gastric secretion.

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Cited by (72)

Stomach Hormones
2020, Hormonal Signaling in Biology and Medicine: Comprehensive Modern Endocrinology
The hormone concept, based upon studies in the upper gastrointestinal tract, was developed more than 100 years ago. The regulation of gastric acid secretion has been a central subject throughout the last century. Leaps were made in the 1960s, with isolation and characterization of new hormones, due to improvement in separation of peptides, and not least, due to the development of immunoassays allowing determination of concentrations in the low picomolar range. Slowly, the role of hormones in clinical gastroenterology was realized: first when diagnosing rare tumors originating from hormone-producing cells, and later when characterizing the pathogenesis of duodenal ulcer caused by Helicobacter pylori. The present overview will focus on the two gastric hormones gastrin and ghrelin. Locally active signal substances working via the paracrine route, like somatostatin and histamine, as well as the neuroendocrine cells producing them, are less thoroughly described. Gastrin is central in gastric physiology by controlling and keeping gastric acidity sufficiently low to allow the killing of swallowed microorganisms, via regulation of enterochromaffin-like cell histamine release as well as proliferation. Infection with H. pylori, as well as drug-induced hypoacidity, results in hypergastrinemia, which in the long term may lead to gastric cancer. Thus, gastrin may play an important role in most diseases of the upper gastrointestinal tract. It is possible that other hormones could have a similar pathogenic role in other locations, where we have less knowledge of the physiology.
Stomach Hormones
2019, Hormonal Signaling in Biology and Medicine: Comprehensive Modern Endocrinology
The hormone concept, based upon studies in the upper gastrointestinal tract, was developed more than 100 years ago. The regulation of gastric acid secretion has been a central subject throughout the last century. Leaps were made in the 1960s, with isolation and characterization of new hormones, due to improvement in separation of peptides, and not least, due to the development of immunoassays allowing determination of concentrations in the low picomolar range. Slowly, the role of hormones in clinical gastroenterology was realized: first when diagnosing rare tumors originating from hormone-producing cells, and later when characterizing the pathogenesis of duodenal ulcer caused by Helicobacter pylori. The present overview will focus on the two gastric hormones gastrin and ghrelin. Locally active signal substances working via the paracrine route, like somatostatin and histamine, as well as the neuroendocrine cells producing them, are less thoroughly described. Gastrin is central in gastric physiology by controlling and keeping gastric acidity sufficiently low to allow the killing of swallowed microorganisms, via regulation of enterochromaffin-like cell histamine release as well as proliferation. Infection with H. pylori, as well as drug-induced hypoacidity, results in hypergastrinemia, which in the long term may lead to gastric cancer. Thus, gastrin may play an important role in most diseases of the upper gastrointestinal tract. It is possible that other hormones could have a similar pathogenic role in other locations, where we have less knowledge of the physiology.
Intracerebroventricular infusion of bombesin modulates GIP secretion in conscious dogs
2010, Neuropharmacology
Citation Excerpt :
Moreover intracerebroventricular administration of BBS was shown to increase serum gastrin levels, and decrease the volume and HCl content of gastric acid (Pappas et al., 1985; Tsalis et al., 1990). In contrast intravenous (i.v.) injection of bombesin in dogs as well as in humans stimulated gastric acid secretion through gastrin dependent mechanisms, indicating a distinct central action of bombesin when injected into the CSF (Varner et al., 1981). Glucose-dependent insulinotropic polypeptide (GIP) is a potent incretin and plays an important role in blood glucose homeostasis.
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin with important role in glucose homeostasis and energy conservation. Thus far, the neural mechanisms involved in the regulation of GIP secretion, have not yet been fully elucidated. The aim of this study was to evaluate a possible effect of intracerebroventricular administration of Bombesin in the regulation of GIP secretion.
Thirty-two adult dogs were used in this study. In group 1 the animals received a bolus icv infusion of 200 ng bombesin or an equivalent amount of artificial cerebrospinal fluid (aCSF). In group 2 the animals received a continuous icv infusion of bombesin or aCSF over a 3-h period. In group 3 the experiment of group 2 was repeated with a simultaneous intraduodenal infusion of a glucose load through the Mann–Bollman fistula. Blood samples were taken from cannulation of a hind limb and plasma levels of glucose, insulin and GIP were assayed.
Bolus icv infusion of bombesin produced an increase in glucose and GIP levels without a respective increase in plasma insulin levels. Continuous icv infusion and the simultaneous infusion of glucose intraduodenally increased significantly GIP, glucose and insulin levels.
Intracerebroventricular levels of bombesin seems to involve in the neural regulation of GIP secretion independently of the presence of nutrients and to potentiate GIP secretion during a glucose load.
Effects of cholecystokinin and bombesin on the expression of preprosomatostatin-encoding genes in goldfish forebrain
2004, Regulatory Peptides
It was previously demonstrated that both cholecystokinin (CCK) and bombesin (BBS) stimulate growth hormone (GH) secretion in goldfish. Both peptides induce satiety and it was speculated that they integrate satiation and the postprandial increase in GH circulating levels. In the present paper we investigated the effects of CCK and BBS on the forebrain expression of the somatostatin gene family in goldfish to analyze if somatostatin peptides may be part of the effector mechanisms of CCK and BBS. We found that peripherally as well as centrally administered CCK decreases mRNA levels of preprosomatostatin (PSS)-I that encodes for SRIF-14, having no effects on PSS-II and PSS-III, which encode for gSRIF-28 and [Pro²] SRIF-14, respectively. In addition, a direct action on the pituitary to stimulate GH release, this inhibition of PSS-I expression provides a possible mechanism for CCK to increase postprandial GH levels. On the other hand, BBS inhibits the forebrain expression of PSS-I and PSS-II but does not affect PSS-III regardless of the route of administration. We conclude that this could be the most likely mechanism of action of BBS to increase GH secretion, since there are few BBS-immunoreactive (IR) fibers and BBS binding sites in the anterior pituitary of goldfish.
Bombesin and the brain-gut axis
2000, Peptides
Bombesin is the first peptide shown to act in the brain to influence gastric function and the most potent peptide to inhibit acid secretion when injected into the cerebrospinal fluid (CSF) in rats and dogs. Bombesin responsive sites include specific hypothalamic nuclei (paraventricular nucleus, preoptic area and anterior hypothalamus), the dorsal vagal complex as well as spinal sites at T9-T10. The antisecretory effect of central bombesin encompasses a variety of endocrine/paracrine (gastrin, histamine) or neuronal stimulants. Bombesin into the CSF induces an integrated gastric response (increase in bicarbonate, and mucus, inhibition of acid, pepsin, vagally mediated contractions) enhancing the resistance of the mucosa to injury through autonomic pathways. The physiological significance of central action of bombesin on gastric function is still to be unraveled.
Role of vagal fibers and bombesin/gastrin-releasing peptide-neurons in distention-induced gastrin release in rats
1997, Regulatory Peptides
In the rat the exact role of vagal fibers and the interaction between the extrinsic and intrinsic neural system in distention-induced gastrin release are still a matter of debate. Accordingly, the aim of the present study was to examine the contribution of afferent and efferent vagal fibers as well as intrinsic neurons on gastrin response to gastric distention.
In anesthetized rats graded gastric distention by 5, 10 and 15 ml saline for 20 min caused a significant volume-dependent increase of plasma gastrin levels by 12±6 pg/ml (5 ml saline, n=8, P=0.05), 26±7 pg/ml (10 ml saline, n=10, P<0.05) and 37±7 pg/ml (15 ml saline, n=8, P<0.01), respectively. To examine the role of the extrinsic vagal innervation, gastrin response to distention was studied in anesthetized rats after bilateral truncal vagotomy (n=9) or selective afferent vagotomy following pretreatment with capsaicin (n=6). Stimulation of gastrin release by 10 ml distention in sham-operated control rats was reversed to an inhibition after truncal vagotomy (26±7 vs. −11±4 pg/ml; P<0.05) and capsaicin-treatment (37±18 vs. −34±11 pg/ml; P<0.05). A contribution of cholinergic mechanisms to this vagovagal-mediated stimulation of distention-induced gastrin release was excluded, since atropine (100 μg/kg/h; n=8) further augmented distention-stimulated gastrin release. Since bombesin/gastrin-releasing peptide (GRP)-neurons contribute to vagally stimulated gastrin secretion, we have examined gastrin response to distention in the presence of the specific bombesin-receptor antagonist d-Phe⁶-BN(6-13)OMe (400 μg/kg/h; n=10). This bombesin-antagonist completely reduced distention-stimulated gastrin release in vivo.
In contrast, distention of the isolated, extrinsically denervated stomach significantly decreased gastrin release by 13±5 pg/min (5 ml saline, n=8, P<0.05), 28±8 pg/min (10 ml saline, n=11, P<0.05) and 35±10 pg/min (15 ml saline, n=8, P<0.01), respectively, without changing the activity of bombesin/GRP-neurons. Distention-induced decrease of gastrin release was attenuated to 50 percent by atropine (10⁻⁷ M; n=10) or tetrodotoxin (TTX) (10⁻⁶ M; n=10), respectively.
These data demonstrate, that in anesthetized rats distention-stimulated gastrin secretion depends on the activation of a vagovagal reflex and intrinsic bombesin/ GRP-neurons. In contrast distention of the isolated rat stomach inhibits gastrin release in part via intrinsic cholinergic pathways and other as yet unknown mechanisms.

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High potency of bombesin for stimulation of human gastrin release and gastric acid secretion

Abstract

Neuroscience

Biochem. Biophys. Res. Commun.

Effect of bombesin on extragastric gastrin in man

Dig. Dis.

Preliminary data on the inhibition of pentagastrin stimulated gastric secretion induced by some natural and synthetic peptides

Br. J. Pharmacol.

Gastrin release by bombesin in the dog

Br. J. Pharmac.

Neuropeptides in the gut and other peripheral tissues

Occureence and polymorphism of bombesin-like peptides in the gastrointestinal tract of birds and mammals

Gut