Somatostatin analogue inhibition of isolated parietal cell secretion

Abstract

Somatostatin, somatotropin release-inhibiting factor (SRIF), is a regulatory peptide that has proved to directly inhibit parietal cell acid secretion. However, the therapeutic usefulness of SRIF has been limited by a brief plasma half-life. Several analogues of SRIF that are effective in suppressing acid secretion in vivo have been developed. This study was undertaken to compare the effects of SRIF and two analogues, SMS 201-995 and L-363,568, on in vitro acid secretion. We used isolated rabbit parietal cells prepared by collagenase digestion and counterflow elutriation. Acid secretion was assessed by the accumulation of 14C-aminopyrine within the cells. Two types of secretagogues were utilized: histamine (10(-6) mol/L), a membrane receptor agonist which acts by means of adenylate cyclase and cyclic AMP, and forskolin (10(-6) mol/L), a direct activator of adenylate cyclase. SRIF, SMS 201-995, and L-363,568 (10(-11) to 10(-7) mol/L) all significantly inhibited histamine-stimulated 14C-AP uptake (p less than 0.001). On a molar basis, SMS 201-995 was 10 times more potent and L-363,568 was 40 times more potent than SRIF. SRIF, SMS 201-995, and L-363,568 significantly inhibited forskolin-stimulated 14C-AP uptake (p less than 0.005). The inhibitory effects of SRIF and both analogues on forskolin-stimulated acid secretion was, however, significantly less than that observed with histamine (p less than 0.05). These results demonstrate increased in vitro potency of SRIF analogues compared with the native peptide. The data are consistent with the hypothesis that SRIF and its analogues function at more than one site within the parietal cell.