Gastric somatostatin release: evidence for direct mediation by calcitonin gene-related peptide and vasoactive intestinal peptide.
It has previously been demonstrated that somatostatin (SRIF) directly inhibits parietal cell secretion. However, the significance of SRIF as a paracrine agent and mechanisms of local gastric SRIF release are not clear. Vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) are neuropeptides which have been localized in the gastric fundus and have been demonstrated to inhibit gastric acid secretion in vivo. The present study examines the hypothesis that CGRP and VIP act via the release of gastric fundic SRIF. The study utilized rabbit isolated gastric glands prepared by collagenase digestion. Glands were incubated alone, or with 10(-10)-10(-6) M CGRP or 10(-10)-10(-6) M VIP for 30 min. Supernatant SRIF was measured using a specific radioimmunoassay. Unstimulated SRIF release was 101 +/- 16 fmole/ml. CGRP (10(-7) and 10(-6) M) and VIP (10(-7) and 10(-6) M) resulted in significant SRIF release. The maximum release of SRIF by CGRP (506 +/- 113 fmole/ml) was significantly greater than that by VIP (293 +/- 33 fmole/ml) (P less than 0.05). However, both these concentrations of SRIF are comparable to the ID50 concentration (4.5 X 10(-10) M) for SRIF inhibition of acid secretion by isolated parietal cells as assessed by [14C]aminopyrine accumulation. These results are consistent with the hypothesis that CGRP and VIP inhibition of acid secretion may be mediated, at least in part, by the local release of SRIF from the gastric fundus. These data further support the significance of paracrine interactions in the modulation of cellular secretory function.
D000818:Animals; D015740:Calcitonin Gene-Related Peptide; D005753:Gastric Mucosa / Q000378:metabolism*; D066298:In Vitro Techniques; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D010295:Parietal Cells, Gastric / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism*; D013268:Stimulation, Chemical; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology / Q000502:physiology*
D009479:Neuropeptides; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D015740:Calcitonin Gene-Related Peptide