Gastrin-releasing peptide: neuronal distribution and spatial relation to endocrine cells in the human upper gut

Sjövall, M.; Ekblad, Eva; Lundell, Lars; Sundler, F.

doi:10.1016/0167-0115(90)90063-3

Cited by 18 publications

(5 citation statements)

References 27 publications

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“…These hormones do not, however, seem to mediate the trophic action of bombesin on the pancreas because the blockade of specific receptors for gastrin and CCK failed to affect the increase in DNA synthesis by this pep tide. This is in keeping with pervious find ings that bombesin exerts direct action pre dominantly on pancreatic secretion and tis sue growth without mediation of gastrin or CCK [24,37], Bombesin-like immunoreactivity has been found in the brain and in the nerves of the gastrointestinal tract and the pancreas [9,10,38], This widespread distribution of bombe sin suggests that the peptide may play an important role in the control of gastrointesti nal functions. Despite the fact that exoge nous bombesin administered for 48 h was found to stimulate DNA synthesis, the block ade of bombesin receptors by a specific antagonist failed to affect refeeding-induced DNA synthesis.…”

Section: Discussionsupporting

confidence: 89%

Antagonism of Receptors for Bombesin, Gastrin and Cholecystokinin in Pancreatic Secretion and Growth

et al. 1991

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The effects of bombesin, gastrin and cholecystokinin (CCK) on amylase secretion from the isolated rat pancreatic acini and on DNA synthesis (as biochemical indicator of trophic action) in the pancreas have been examined in 48-hour fasted and 16-hour refed rats with and without administration of specific receptor antagonists for bombesin, gastrin and CCK. Studies on the isolated rat acini revealed that bombesin, gastrin and CCK-8 all showed the same efficacy in their ability to stimulate amylase release. RC-3095, bombesin pseudopeptide antagonizing bombesin receptors, was effective only in suppressing the amylase response to bombesin but not to gastrin or CCK. Benzodiazepine receptor antagonists for gastrin (L-365,260) and for CCK (L-364,718) showed higher efficacy in the inhibition of amylase release induced by pentagastrin and CCK, respectively, but failed to affect that induced by bombesin. These peptides administered 3 times daily for 48 h in fasted rats increased the rate of DNA synthesis as measured by the incorporation of [³H]thymidine into DNA. The blockade of bombesin receptors abolished the DNA synthesis induced only by bombesin but not by gastrin or CCK. The blockade of gastrin receptors by L-365,260 suppressed the DNA synthesis induced by gastrin while the antagonism of CCK receptors by L-364,718 was effective only against CCK. Refeeding of 48-hour fasting rats strongly enhanced DNA synthesis which was significantly reduced by blocking only the CCK receptors (with L-364,718), but not the bombesin (with RC-3095) or gastrin receptors (with L-365,260). This study indicates that the secretory stimulation of pancreatic acini and DNA synthesis can be achieved by exogenous bombesin, gastrin and CCK acting via separate receptors, but that only CCK plays the major role in the postprandial stimulation of the growth of pancreatic tissue.

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Section: Discussionsupporting

confidence: 89%

Antagonism of Receptors for Bombesin, Gastrin and Cholecystokinin in Pancreatic Secretion and Growth

et al. 1991

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“…The delay observed in the secretion of gGLI induced by electrical stimulation was very similar to that observed in the experiments involving fat-induced secretion in gut-transected animals. GRP is localized extensively in the myenteric plexus (32) and potently stimulates the secretion of GLP-1 (8,11,12). The delay may also occur due to involvement of a peptidergic mediator in the efferent signaling pathway, as the effects of these neuromodulators are known to be preceded by long latent periods (31).…”

Section: Discussionmentioning

confidence: 99%

Role of the Vagus Nerve in Mediating Proximal Nutrient-Induced Glucagon-Like Peptide-1 Secretion*

1999

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Plasma levels of glucagon-like peptide-1 (GLP-1) rise rapidly after nutrient ingestion, suggesting the existence of a proximal gut signal regulating GLP-1 release from the L cells of the distal small intestine. Glucose-dependent insulinotropic peptide (GIP) has been shown to be one such proximal signal; however, the dependence of GIP on gastrin-releasing peptide, a neuromodulator, suggested a role for the nervous system in this proximal-distal loop. Investigations into the nature of this proximal signal were therefore conducted in an in situ model of the rat gastrointestinal system. Infusions of corn oil into a 10-cm segment of duodenum that was isolated by loose ligation (to ensure that the luminal contents did not progress to the ileal L cell) increased the secretion of GLP-1 in parallel with that of gut glucagon-like immunoreactivity (gGLI; r = 0.85; P < 0.05). Infusion of fat into a transected segment of duodenum also significantly raised gGLI secretion compared with saline infusion, reaching a peak value of 132 +/- 37 pg/ml above basal (P < 0.05). However, peak secretion was significantly delayed when the gut was transected compared with that after ligation alone (19 +/- 4 vs. 6 +/- 1 min, respectively; P < 0.05). Furthermore, bilateral subdiaphragmatic vagotomy in conjunction with gut transection completely abolished the fat-induced rise in gGLI secretion (P < 0.001). Consistent with a role for the vagus in the regulation of the L cell, stimulation of the distal end of the celiac branch of the subdiaphragmatic vagus nerve significantly stimulated the secretion of gGLI to a level of 71 +/- 14 pg/ml above basal (P < 0.05). As found previously, supraphysiological infusion of GIP significantly increased gGLI secretion in control animals by 123 +/- 32 pg/ml (P < 0.05); this was not prevented by hepatic branch vagotomy (96 +/- 25 pg/ml; P < 0.05). In contrast, although infusion of GIP at physiological levels into sham-vagotomized animals also increased gGLI secretion, by 40 +/- 6 pg/ml (P < 0.05), selective hepatic branch vagotomy abolished GIP-induced gGLI secretion (P < 0.05). The results of these experiments therefore demonstrate that the secretion of GLP-1 and gGLI from the ileal L cell in response to fat is regulated by a complex neuroendocrine loop, involving the enteric nervous system, the afferent and efferent vagus nerves, as well as the duodenal hormone GIP.

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“…The gastrin-releasing property of GRP has been suggested to be mediated via a direct effect of GRP on the antral gastrin cells [11]. However, we have recently observed that in the human antral mucosa, few GRP containing nerve fibres were seen in the gastrin cell region, pointing towards mechanisms of GRP-induced gastrin release alternative to a direct GRP innervation of gastrin cells [12], As is the case with food-induced gastrin release, cholinergic blockade also facilitates the gas trin releasing property of GRP in duodenal ulcer patients, an effect exerted also by dener vation of the oxyntic cell area of the stomach [9], These observations altogether would sug gest that the mechanisms regulating the re lease of antral gastrin are more complex than previously suggested, involving both inhibi tory and stimulatory mechanisms of which some may be conveyed via vagal fibres. The lack of intimate spatial interrelationship be tween GRP containing nerve fibres and gas trin cells may also suggest an indirect mode of action of GRP with involvement of interneu rons.…”

Section: Discussionmentioning

confidence: 79%

Defective Inhibition of Gastrin Release by Antral Distension in Duodenal Ulcer Patients

Sjövall¹,

Lindstedt

Olbe

et al. 1992

Digestion

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The gastrin response to a low and a high dose of gastrin-releasing peptide infusion was studied in healthy volunteers and in patients with duodenal ulcer disease. In duodenal ulcer patients, the gastrin response was exaggerated. Cholinergic blockade did not change the gastrin release in healthy volunteers. Antrum distension during neutralization of the gastric lumen was unable to stimulate gastrin release, also under cholinergic blockade. However, in healthy volunteers distension of the antrum significantly inhibited the gastrin response to gastrin-releasing peptide infusion. This inhibitory influence was most pronounced in patients given the lower dose of the neuropeptide. Cholinergic blockade counteracted the inhibitory effect exerted by antral distension. On the other hand, antral distension did not alter the gastrin response to gastrin-releasing peptide in patients with duodenal ulcer disease. These results suggest an additional defective inhibitory mechanism in duodenal ulcer patients.

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Gastrin-releasing peptide: neuronal distribution and spatial relation to endocrine cells in the human upper gut

Cited by 18 publications

References 27 publications

Antagonism of Receptors for Bombesin, Gastrin and Cholecystokinin in Pancreatic Secretion and Growth

Antagonism of Receptors for Bombesin, Gastrin and Cholecystokinin in Pancreatic Secretion and Growth

Role of the Vagus Nerve in Mediating Proximal Nutrient-Induced Glucagon-Like Peptide-1 Secretion*

Defective Inhibition of Gastrin Release by Antral Distension in Duodenal Ulcer Patients

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