INTRACEREBROVENTRICULAR INJECTION OF SOMATOSTATIN SST(5) RECEPTOR AGONIST INHIBITS GASTRIC-ACID SECRETION IN RATS

Somatostatin and its analogs act in the brain to influence gastric aci d secretion. Five different somatostatin receptor subtypes have been c haracterized (sst(1) to sst(5)). We studied the influence of somatosta tin (0.18-0.6 nmol/rat) and selective sst,, sst, and sst, receptor lig ands on basal gastric acid secretion in conscious rats equipped with c hronic gastric and intracereb roventricular (i.c.v.) cannulae. Somatos tatin-14 (0.36 nmol/rat), the sst(2), sst(3) and sst(5) receptor agoni st, A(1,2,4,5,12,13)-[D-Tryp(8),D-Cys(14)]somatostatin (SMS 201-995) ( 0.18-0.36 nmol/rat) and the sst, receptor agonist, BIM-23052, (0.8-1.2 nmol/rat) injected i.c.v. inhibited gastric acid secretion. Maximal i nhibition reaching 42%, 60% and 42% was induced by somatostatin-14 (0. 36 nmol/rat), SMS 201-995 (0.18 nmol/rat) and BIM-23052 (0.8 nmol/rat) respectively. The sst(2) receptor agonist, DC 32-87 (0.2-0.8 nmol/rat ) and sst, receptor agonist, BIM-23056 (0.2-1.2 nmol/rat), did not mod ify gastric acid secretion, except the sst(3) receptor agonist at 0.4 nmol/rat which increased acid output at 20 min post-injection. The sst (2) receptor agonists (0.4 nmol/rat) co-injected i.c.v with a subthres hold dose of sst(5) (0.4 nmol/rat) inhibited gastric acid secretion. T hese results show that i.c.v. injection of somatostatin-14 inhibits ba sal gastric acid secretion in conscious rats through an action on sst( 5) receptor subtype which can be potentiated by sst(2) receptor subtyp e.