SOMATOSTATIN SST(2) RECEPTOR-MEDIATED INHIBITION OF PARIETAL-CELL FUNCTION IN RAT ISOLATED GASTRIC-MUCOSA

1 The aim of this study was to determine the location and functional c haracteristics of the somatostatin (SRIF) receptor type(s) which media te inhibition of acid secretion in rat isolated gastric mucosa. 2 Gast rin (1 nM-1 mu M), dimaprit (10 mu M-300 mu M) and isobutyl methylxant hine (IBMX, 1 mu M-100 mu M) all caused concentration-dependent increa ses in acid output. Responses to gastrin were almost completely inhibi ted by ranitidine (10 mu M) at a concentration which abolished the sec retory response to dimaprit. In contrast, responses to IBMX were not c hanged by ranitidine suggesting that IBMX acts directly on the parieta l cell and not indirectly by releasing histamine from enterochromaffin -like (ECL) cells. 3 SRIF-14 (1 nM-1 mu M) had no effect on basal acid output, but inhibited acid output produced by gastrin, dimaprit and I BMX in a concentration-dependent manner with respective EC(50) values of 46, 54 and 167 nM. The peptidase inhibitors, amastatin (10 mu M) an d phosphoramidon (1 mu M), had no effect on SRIF-induced inhibition of dimaprit stimulated gastric acid secretion. 4 The inhibitory effect o f a range of SRIF analogues on gastrin-, dimaprit- and IBMX-induced ac id secretion was also studied. Irrespective of the secretagogue used t o increase acid output, the rank order of potencies was similar 7=segl itide=octreotide>SRIF-14=SRIF-28>L-362,855). The linear peptide BIM-23 056 was devoid of agonist or antagonist activity in concentrations up to 1 mu M. 5 The sst(2) receptor selective peptides, BIM-23027, seglit ide and octreotide were the most potent inhibitors of gastrin-, dimapr it- and IBMX-induced acid secretion suggesting that SRIF receptors res embling the recombinant sst, receptors are involved. Furthermore, sinc e dimaprit and IBMX stimulate gastric acid secretion independently of histamine release, sst, receptor-mediated inhibition must occur at the level of the parietal cell itself.