Central nervous system action of bombesin to inhibit gastric acid secretion

Bombesin or gastrin releasing peptide injected into the lateral, third, or fourth ventricle, or into the cisterna magna, inhibited gastric acid secretion induced by a wide variety of gastric acid stimulants in several animal models. Studies of bombesin microinfusion into specific hypothalamic nuclei of intact rats, or injection into the cisterna magna of midbrain transected rats, indicated that the peptide can trigger inhibition of gastric acid secretion from both forebrain and hindbrain structures. The neural pathways mediating bombesin action required the integrity of the cervical spinal cord; the vagus did not play an important role. Spantide, a substance P and bombesin receptor antagonist, was not useful in studying the physiological role of bombesin. This was due both to its inability to reverse the central action of bombesin on gastric secretion, and to its in vivo toxicity.     

Effects of spantide on guinea pig coronary resistance vessels.

Effects of spantide ([D-Arg1,D-Trp7,9,Leu11]substance P) on coronary resistance vessels were studied in isolated guinea pig hearts perfused at constant rate with isotonic buffer containing 20 or 40 mM KCl. Spantide (1 microM) caused a 20-fold rightward shift of the substance P (SP) dose-response curve for vasodilation with no change in maximum (KB = 5.3 x 10(-8) M). Bolus injections of 0.25 to 250 pmol spantide had no effect, but higher doses caused a brief vasodilation followed by a larger, more prolonged vasoconstriction. Histamine produced similar changes in perfusion pressure. Antihistamines (H1 and H2) reduced or blocked responses to spantide and histamine. These findings indicate spantide is a competitive antagonist to SP in guinea pig coronary resistance vessels. In addition, high doses of spantide can cause prominent vascular effects which are mediated by histamine.     

Differentiation of multiple neurokinin receptors in the guinea pig ileum

We have studied the selectivity and competitiveness of three neurokinin antagonists and atropine against substance P, neurokinin A, and neurokinin B. DPDTNLE-NB, [D-Pro2, D-Trp6,8, Nle10]-neurokinin B is a competitive antagonist of neurokinin B (pA2 = 5.5), but not substance P or neurokinin A. DPDT-SP ([D-Pro2,Trp7,9]-substance P), competitively blocks substance P (pA2 = 6.9) and neurokinin B (pA2 = 6.8), but not neurokinin A. Spantide ([D-Arg1, D-Trp7,9, Leu11]-substance P) competitively blocks substance P (pA2 = 6.7) and at a log unit higher concentration blocks neurokinin A (pA2 = 5.8), but does not block neurokinin B. Atropine is a competitive antagonist of neurokinin B (pA2 = 9.0) at ten times the concentration needed to block acetylcholine (pA2 = 10.1), but does not inhibit the other neurokinins. These results support the hypothesis of multiple neurokinin receptors in the guinea pig ileum and indicate that the site of neurokinin B, but not substance P or neurokinin A is predominantly on intramural neurons. This indirect stimulation appears to be dependent on the release of acetylcholine. Neurokinin B also has activity on smooth muscle receptors since the contractile response could not be completely antagonized by atropine. There appear to be two smooth muscle neurokinin receptors on the basis of results obtained with DPDT-SP and spantide, one predominantly responsive to substance P and the other to neurokinin A. Only spantide appeared to have any effect on the neurokinin A receptor and that was at a much higher concentration than that needed to block substance P.     

Stimulation of canine pancreatic polypeptide, gastrin, and gastric acid secretion by ranatensin, litorin, bombesin nonapeptide and substance P

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.     

The effects of antagonists of receptors for gastrin, cholecystokinin and bombesin on growth of gastroduodenal mucosa and pancreas.

The effects of gastrin, cholecystokinin (CCK) and bombesin on the DNA synthesis, as a biochemical indicator of trophic action in the gastroduodenal mucosa and the pancreas have been examined in rats fasted for 48 h and in rats refed for 16 h with or without administration of specific receptor antagonists for bombesin, gastrin and CCK. Bombesin and gastrin administered three times daily for 48 h in fasted rats significantly increased the rate of DNA synthesis as measured by the incorporation of [3H] thymidine into DNA in each tissue tested. CCK significantly increased DNA synthesis in the duodenal mucosa and pancreatic tissue, but not in the gastric mucosa. The stimulation of DNA synthesis induced by bombesin in the gastroduodenal mucosa and pancreas was abolished by bombesin/GRP receptor antagonist, RC-3095. RC-3095 did not affect DNA synthesis stimulated by gastrin and CCK in these tissues. L-365,260, a receptor antagonist for gastrin suppressed the DNA synthesis induced by gastrin but not by CCK or bombesin in the gastrointestinal mucosa and pancreas. L-364,718 a specific antagonist for CCK receptors was effective only against CCK stimulated duodenal mucosa and pancreatic growth. Refeeding of 48 h fasting rats strongly enhanced the DNA synthesis in all tissues tested, and this effect was significantly reduced in the gastroduodenal mucosa by blocking only gastrin receptors (with L-365,260) and that in the duodenal mucosa and the pancreas by antagonizing of CCK receptors (with L-364,718). Antagonism of bombesin receptors (with RC-3095) did not significantly affect the stimulation of DNA synthesis induced by refeeding in all tissues tested. This study indicates that the stimulation of DNA synthesis can be achieved by exogenous gastrin, CCK and bombesin acting through separate receptor but that only gastrin and CCK play the major role in the postprandial stimulation of the growth of gastroduodenal mucosa and pancreatic tissue.     

The antagonism of bombesin in the CNS by substance P analogues

The ability of substance P analogues to inhibit the action of bombesin in the CNS was investigated using receptor binding and biological assays. The putative substance P antagonists inhibited binding to central receptors for both substance P and bombesin-like peptides. Spantide, which was the most potent analogue tested, reversed the bombesin induced hypothermia and grooming. Therefore the putative substance P antagonists may also antagonize the actions of bombesin in the CNS     

Bombesin-like peptides elevate cytosolic calcium in small cell lung cancer cells

The ability of bombesin-like peptides to elevate intracellular Ca2+ levels in small cell lung cancer cells was investigated using the fluorescent Ca2+ indicator Fura 2. Nanomolar concentrations of bombesin elevated cytosolic Ca2+ levels in the absence or presence of extracellular Ca2+. Potent bombesin receptor agonists, such as gastrin releasing peptide (GRP) or (GRP)14-27 elevated cytosolic Ca2+ levels whereas inactive compounds such as (D-Trp8)bombesin or (GRP)1-16 did not. Furthermore, the bombesin receptor antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11) substance P (30 microM) had no effect on the Ca2+ levels by itself but antagonized the increase in Ca2+ caused by 10 nM or 100 nM bombesin. These data suggest that bombesin receptors may regulate the release of Ca2+ from intracellular organelles in small cell lung cancer cells.     

The effect of antagonist of receptors for gastrin, cholecystokinin and bombesin on growth of gastroduodenal mucosa and pancreas.

The effects of gastrin, cholecystokinin (CCK) and bombesin on the DNA synthesis, as a biochemical indicator of trophic action in the gastroduodenal mucosa and the pancreas, have been examined in rats fasted for 48 h and in rats refed for 16 h with or without administration of specific receptor antagonists for bombesin, gastrin and CCK. Bombesin and gastrin administered three times daily for 48 h in fasted rats significantly increased the rate of DNA synthesis as measured by the incorporation of [3H] thymidine into DNA in each tissue tested. CCK significantly increased DNA synthesis in the duodenal mucosa and pancreatic tissue, but not in the gastric mucosa. The stimulation of DNA synthesis induced by bombesin in the gastroduodenal mucosa and pancreas was abolished by bombesin/GRP receptor antagonist, RC-3095. RC-3095 did not affect DNA synthesis stimulated by gastrin and CCK in these tissues. L-365,260, a receptor antagonist for gastrin suppressed the DNA synthesis induced by gastrin but not by CCK or bombesin in the gastrointestinal mucosa and pancreas. L-364,718, a specific antagonist for CCK receptors was effective only against CCK stimulated duodenal mucosa and pancreatic growth. Refeeding of 48 h fasting rats strongly enhanced the DNA synthesis in all tissues tested, and this effect was significantly reduced in the gastroduodenal mucosa by blocking only gastrin receptors (with L-365, 260) and that in the duodenal mucosa and the pancreas by antagonizing of CCK receptors (with L-364,718). Antagonism of bombesin receptors (with RC-3095) did not significantly affect the stimulation of DNA synthesis induced by refeeding in all tissues tested. This study indicates that the stimulation of DNA synthesis can be achieved by exogenous gastrin, CCK and bombesin acting through separate receptors, but that only gastrin and CCK play the major role in the postprandial stimulation of the growth of gastroduodenal mucosa and pancreatic tissue.     

Reduced peptide bond pseudopeptide analogues of substance P. A new class of substance P receptor antagonists with enhanced specificity

Each of the last 6 peptide bonds in the COOH terminus of [Leu11]substance P [( Leu11]SP) and [Nle11]spantide were replaced with [CH2NH], and each analogue was tested for SP agonist or antagonist activity by determining its ability to interact with SP receptors on dispersed acini from guinea pig pancreas. Each of the 6 spantide and 5 of the 6 SP analogues had no agonist activity, whereas [psi 9-10]SP was an agonist. For the spantide pseudopeptides, the psi 10-11 analogue (Ki,2.8 microM) was equipotent as an antagonist to spantide itself, whereas the psi 9-10, psi 8-9, psi 7-8, and psi 6-7 analogues were 2.5, 7, 5, and 3 times less potent. For the SP pseudopeptides, the psi 10-11 analogue was the most potent antagonist (Ki, 6.2 microM), whereas the psi 8-9, psi 7-8, and psi 6-7 analogues were 7-, 36-, and 39-fold less potent. There was a close correlation between the ability of each pseudopeptide to inhibit binding of 125I-Bolton-Hunter-SP and to affect amylase secretion. [psi 10-11]SP inhibited SP-stimulated amylase release in a competitive manner, and its inhibitory ability was specific for the SP receptor. Despite [psi 10-11]SP, spantide, and [psi 10-11]spantide having similar affinities for the SP receptor (Ki, 2-6 microM), for inhibition of binding of 125I-[Tyr4]bombesin, the analogues differed with [psi 10-11]SP having a 50-fold lower affinity than for the SP receptor, whereas [psi 10-11]spantide had a 4-fold lower affinity and spantide a 1.5-fold lower affinity for the SP receptor. These results demonstrate that SP pseudopeptides represent a new class of SP receptor antagonists and, in contrast to the currently described SP receptor antagonists, are more specific for SP receptors.     

Comparison of spantide II and CP-96,345 for blockade of tachykinin-evoked contractions of smooth muscle.

CP-96,345, a quinuclidine, is a potent inhibitor of substance P for the NK1 receptor of bovine brain, but has reduced potency for the corresponding receptor of the rat and mouse, and none for NK2 or NK3 receptors. A related quinuclidine showed similar but lower potency than CP-96,345 for NK1. CP-96,345 was more potent than the spantide I of 1984, D-Arg1,Pro2,Lys3,Pro4,Gln5,Gln6,D-Trp7,Phe8,D-Trp9, Leu10,Leu11,NH2. Our continued designs for antagonists of substance P led to spantide II in 1990 which is: D-NicLys1,Pro2,3-Pal3,Pro4,D-Cl2Phe5,Asn6,D-Trp7 ,Phe8,D-Trp9,Leu10,Nle11-NH2. The pA2 values of spantide II and CP-96,345 for guinea pig taenia coli were 7.6 and 6.8, respectively. The pIC50 values for blockade of tachykinin-mediated neurotransmission in the rabbit iris sphincter were 6.1 and 5.4, respectively. Spantide II was nearly 10 times more potent than CP-96,345 in these two assays.     

C-terminal peptides of calcitonin gene-related peptide act as agonists at the cholecystokinin receptor

We have previously described that [Tyr⁰]CGRP(28–37) acts as a receptor antagonist of rat CGRP in guinea pig pancreatic acini. We therefore examined other C-terminal peptides of CGRP for such activity. CGRP-acetyl(28–37) acetate did act as a rat CGRP antagonist. However, C-terminal CGRP peptides of 4 to 8 amino acid residues did not antagonize the actions of rat CGRP but stimulated amylase secretion. In pancreatic acini, a maximally effective concentration of rat CGRP (100 nM) caused a 2.1-fold increase in amylase secretion. When the C-terminal peptides of CGRP were tested in at 100 μM, CGRP(34–37) caused a 1.8-fold increase in amylase secretion, CGRP(33–37) a 2.8-fold increase, CGRP(32–37) a 9.2-fold increase, CGRP(31–37) a 4.1-fold increase, and CGRP(30–37) a 5.1-fold increase. Further studies with the most effective peptide, CGRP(32–37), demonstrated that it did not cause release of lactate dehydrogenase, and thus did not cause amylase release by cell damage. Unlike rat CGRP, CGRP(32–37) did not increase cellular cyclic AMP, but did stimulate outflux of ⁴⁵Ca. CGRP(32–37)-stimulated amylase release was not inhibited by the substance P receptor antagonist, spantide, by the bombesin receptor antagonist, [D-Phe⁶]bombesin(6–13) propylamide, or by the muscarinic receptor antagonist, atropine, but was inhibited by the CCK receptor antagonist L364,718. C-terminal peptides of CGRP inhibited binding of ¹²⁵I-BH-CCK-8, with the relative potencies of the peptides being the same as their relative potencies for stimulating amylase secretion. The present data demonstrate that C-terminal peptides of CGRP, although they have only 2 amino acid residues in common with CCK(26–33), act exclusively at CCK receptors on pancreatic acini to stimulate amylase secretion.     

Effects of bombesin on behavior

This report describes the influence of bombesin on the gross behavior of goldfish, frogs, mice, rats, guinea pigs, rabbits, chicks, pigeons and monkeys. Goldfish, frogs, chicks and pigeons were overtly unaffected by bombesin given centrally and/or peripherally. Mice, rats, guinea pigs, rabbits and monkeys responded quickly to intracerebroventricular (i.c.v.) and/or intrathecal (i.th.) administration of bombesin by displaying a range of behaviors suggestive of altered skin sensation. In mice, bombesin was essentially equipotent as a scratch inducer by i.c.v. and i.th. routes (A50 = 0.010-0.019 microgram) but 6800 times less potent i.p. In rats, bombesin-induced grooming and scratching behaviors were shown to be qualitatively different from those associated with ACTH-(1-24) and thyrotropin releasing hormone. Spantide and [D-Arg1, D-Pro2, D-Trp7,9, Leu11]substance P (both at 0.20, 0.50 and 0.80 microgram i.c.v.), two proposed bombesin receptor antagonists, did not markedly influence bombesin-induced scratching or hypothermia in rats.     

Inhibition of bombesin-stimulated gastrin release from isolated canine G cells by bombesin antagonists

This study investigated the effects of two putative bombesin antagonists, [D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P and [Leu13-psi-CH2NH-Leu14]bombesin, on bombesin-stimulated gastrin release from isolated canine G cells following short-term culture. Canine antral tissue was dispersed by sequential collagenase and EDTA treatment, and counterflow elutriation was used to enrich for G cells. Plates were seeded with 2 x 10(6) cells/mL in each well and cultured for 2 days prior to testing. Gastrin-containing and somatostatin-containing cells were identified by immunocytochemistry using the biotin-avidin-peroxidase method and accounted for 8.5 and 1%, respectively, of adhered cells. Basal gastrin secretion was 1.91 +/- 0.48% of total cell content. After a 2-h incubation period, bombesin (0.01-100 pM) stimulated gastrin release in a concentration-dependent fashion. The substance P analog, at a concentration of 1 microM, modestly inhibited bombesin-stimulated gastrin release from canine G cells. This analog also produced weak stimulation of basal gastrin release. In contrast, the bombesin analog, at a concentration of 1 microM, did not affect basal gastrin secretion. The bombesin analog completely blocked bombesin-stimulated gastrin release from 0.01 to 1 pM and produced greater than 50% inhibition at higher doses. The ability of the bombesin analog to directly inhibit bombesin-stimulated gastrin release from cultured canine G cells underscores its usefulness in studies involving the role of bombesin and its mammalian counterpart, gastrin-releasing peptide, in the control of gastrin cell function.     

Intravenous histamine reduces bombesin-stimulated gastrin release in dogs

The effect of histamine on gastrin release was studied in 7 conscious mongrel dogs with chronic gastric and duodenal fistulas. Histamine-2 HCl was infused in doses of 0 (control), 20, 40, 80, and 160 micrograms/kg per h for 2 h on separate days. During the second hour, bombesin 500 ng/kg per h was infused intravenously. Intragastric pH was constantly kept at 2.5 by intragastric titration during each test. Leakage of gastric contents into the duodenum was prevented by a prepyloric balloon passed retrograde through a duodenal fistula. Gastrin release, as expressed by the integrated response during the last 50 min of the bombesin infusion was significantly (P less than 0.05) decreased by all doses of histamine, compared to control. The infusion doses of histamine studied, 20, 40, 80, and 160 micrograms/kg per h reduced bombesin-stimulated gastrin release 16%, 19%, 19%, and 30%, respectively. This effect was blocked by a histamine H-2 but not an H-1 receptor antagonist. We conclude that by an H-2 mechanism, exogenous histamine reduces bombesin-stimulated gastrin release in dog.     

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

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.     

Gastrin release after truncal vagotomy in fistula dogs: Hypersensitivity to bombesin but not bethanechol

Integrated gastrin response was measured by the serial changes in serum immunoreactive gastrin after various stimuli in three dogs with gastric fistula and highly selective fundic vagotomy, who were then subjected to truncal vagotomy. Truncal vagotomy eliminated the gastrin as well as the gastric acid response to vagal excitation by 2-deoxy-glucose, but did not significantly change the responses to bethanechol (20 or 120 μg/kg/hr by IV infusion). Acid output was the same with bombesin or its nonapeptide in the dogs with fundic vagotomy as it was after subsequent truncal vagotomy, but gastrin release was very much increased by truncal vagotomy. For a 3-hour infusion of bombesin integrated gastrin release was 65 and 143 ng/ml/min and for its nonapeptide 43 and 109 ng/ml/min in the dogs with fundic and truncal vagotomy respectively. The marked hypersensitivity of the gastrin response after truncal vagotomy to bombesin but not to a cholinergic agonist suggests that the antral denervation led to a post-denervation hyper-response to the putative transmitter, bombesin, and that the vagal release of antral gastrin may thus represent a peptidergic neurohormonal mechanism. Also, a long half-life of effect suggests that bombesin binds avidly to its receptors.     

铃蟾肽(Bombesin)对离体灌流大鼠胃的胃泌素、生长抑素、胰升糖素及胃酸释放的影响

本研究用离体大鼠胃灌流技术来观察铃蟾肽对胃-肠激素及胃酸分泌的影响。2×10~(?)mol/L铃蟾肽以0.3ml/min速度作动脉内输注,可刺激胃酸的分泌,自2.50±0.05×10~(-1)增至5.50±1.50×10~(-1)mEq/min,但与外源性五肽胃泌素无协同作用。铃蟾肽引起两次性的门脉中胃泌索及生长抑素的释放,但抑制胰升糖素释放。这三种激素的基础释放率分别为:胃泌素62±8pg,生长抑素5.9±1.1ng,胰升糖素0.40±0.03ng/min;2×10~(-8)mol/L铃蟾肽以0.3ml/min作动脉内输注,胃泌素及生长抑素的峰值分别为1,000±20pg及12.2±2.0ng/min,胰升糖素的最低值为0.17±0.05ng/min,三种激素的反应均与铃蟾肽的浓度成正比。在胃腔流出液中也可测到上述三种激素,但量要少得多。     

Direct contractile effect of motilin on isolated smooth muscle cells of guinea pig small intestine.

We examined the direct effect of motilin on longitudinal and circular smooth muscle cells isolated from the guinea pig small intestine. In addition, the effects of 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxy-benzoate hydrochloride (TMB-8, an inhibitor of intracellular Ca(2+)-release), verapamil (a voltage-dependent Ca(2+)-channel blocker), and removal of extracellular Ca2+ were investigated to evaluate the role of intracellular Ca2+ stores and extracellular Ca2+ on the muscle contraction induced by motilin. The effects of atropine (a muscarinic receptor antagonist), spantide (a substance P receptor antagonist) and loxiglumide (a CCK-receptor antagonist) were also examined to determine whether the motilin-induced contraction was independent of those receptors. Motilin induced a contraction of the longitudinal and circular smooth muscle cells in a dose-dependent manner with the maximal effect attained after 30 seconds of incubation. The ED50 values were 0.3 nM and 0.05 nM, respectively. TMB-8 suppressed completely the motilin-induced contraction of both types of smooth muscle cells. Verapamil had only a slight suppressive effect. Removal of extracellular Ca2+ did not have any significant influence on motilin-induced contraction. The contractile response to motilin was not affected by atropine, spantide or loxiglumide. Our findings showed that:1) motilin has a direct contractile effect on both longitudinal and circular smooth muscle cells; 2) this contractile effect is not evoked via muscarinic, substance P or CCK receptors, and 3) the intracellular release of Ca2+ plays an important role in the contractile response to motilin on both types of smooth muscle cells.     

Stimulatory effect of endogenous orexin A on gastric emptying and acid secretion independent of gastrin

Orexin A (OXA) increases food intake and inhibits fasting small bowel motility in rats. The aim of this study was to examine the effect of exogenous OXA and endogenous OXA on gastric emptying, acid secretion, glucose metabolism and distribution of orexin immunoreactivity in the stomach. Rats equipped with a gastric fistula were subjected to intravenous (IV) infusion of OXA or the selective orexin-1 receptor (OX1R) antagonist SB-334867-A during saline or pentagastrin infusion. Gastric emptying was studied with a liquid non-nutrient or nutrient, using 51Cr as radioactive marker. Gastric retention was measured after a 20-min infusion of OXA or SB-334867-A. Plasma concentrations of OXA, insulin, glucagon, glucose and gastrin were studied. Immunohistochemistry against OXA, OX1R and gastrin in gastric tissue was performed. OXA alone had no effect on either acid secretion or gastric emptying. SB-334867-A inhibited both basal and pentagastrin-induced gastric acid secretion and increased gastric retention of the liquid nutrient, but not PEG 4000. Plasma gastrin levels were unchanged by IV OXA or SB-334867-A. Plasma OXA levels decreased after intake of the nutrient meal and infusion of the OX1R antagonist. Only weak effects were seen on plasma glucose and insulin by OXA. Immunoreactivity to OXA and OX1R were found in the mucosa, myenteric cells bodies and varicose nerve fibers in ganglia and circular muscle of the stomach. In conclusion, endogenous OXA influences gastric emptying of a nutrient liquid and gastric acid secretion independent of gastrin. This indicates a role for endogenous OXA, not only in metabolic homeostasis, but also in the pre-absorptive processing of nutrients in the gut.     

Evidence that bombesin releases extragastric gastrin in man

Bombesin-induced gastrin release from extragastric sources has been investigated in two groups of patients without gastric antrum: 11 patients with total gastrectomy and 11 patients with subtotal (Billroth II) gastrectomy. A 30-min bombesin infusion (5 ng . kg-1 . min-1) caused a prompt significant gastrin increase (P less than 0.05) in both groups of patients. The gastrin response to bombesin was significantly (P less than 0.005) lower in patients without antral tissue than in the control group (n = 7). The individual peak gastrin responses, in totally (TG) and subtotally (SG) gastrectomized patients, were significantly over basal levels (TG: peak 100.3 +/- 12 vs. basal 62.8 +/- 9.1, P less than 0.005; SG: peak 96.9 +/- 9.4 vs. basal 72.4 +/- 6.8, P less than 0.001; pg/ml, mean +/- S.E.M.). These data indicate that bombesin acts not only on antral G cells, but on all gastrin cells in the gastrointestinal tract.