MATERIALS AND METHODS

We have used isolated canine parietal cells to examine the receptor and postreceptor events mediating the inhibii effects of sumatostatin on acid secretion. Somatostatin-14 (514) and somatostatin-28 (528) dose dependently inhibited parietal cells stim-ulated by secretagogues that activate both the adenylate cyclase/cyclic adenosine monophosphate and the inositol phospholipid/ protein kinase C cascades. The inhibitory action was mediated via a specific cell surface receptor that consists of a single subunit protein (molecular weight §g,ooO d). This receptor recognized S14 and S28 equally well. Sornatostatin inhiied parfetal cell activity via mechanisms that are both dependent on and independent of a pertussis toxin-sensitive inhibitory guanine nucleotide binding protein. 0 1999 by W.3. Smmders Company. S INCE ITS initial isolation from sheep hypothalamus, ’ somatostatin has been found in many areas throughout the body including the gastric mucosa.2 Both in vivo and in vitro studies have demonstrated that somatostatin is released into the circulation in response to nutrient ingestion, ’ reach-ing plasma concent~tions that are sufficient o inhibit gastric acid secretion.4 In addition, somatostatin containing D-cells, which are found throughout he fundic mucosa, contain long cytoplasmic processes ’ extending to parietal cells, suggesting a local or paracrine regulatory role for this peptide on acid secretory cell function. Despite the abundance ofin vitro and in vivo studies examining the effect of somatostatin on acid secretion, its direct action on parietal cell function continues to be a source of debate. The present studies demonstrate our efforts to elucidate the receptor and postreceptor events important in mediating somatostatin’s regulatory action on parietal cells