PRESYNAPTIC MODULATION BY VIP, SECRETIN AND ISOPROTERENOL OF SOMATOSTATIN RELEASE FROM ENRICHED ENTERIC SYNAPTOSOMES - ROLE OF CAMP

The release of somatostatin-like immunoreactivity was studied in isola ted enteric synaptosomes. A significant release of somatostatinlike im munoreactivity was observed in the presence of vasoactive intestinal p olypeptide (VIP) (10(-6) M: 53.0 +/- 12.4 pg/mg, basal: 14.3 +/- 1.7 p g/mg, n = 5, P < 0.05), secretin(10(-6) M: 56.1 +/- 3.8 pg/mg, basal: 25.8 +/- 1.6 pg/mg, n = 6, P < 0.01) and isoproterenol (10(-5) M: 54.0 +/- 13.4 pg/mg, basal: 20.0 +/- 3.4 pg/mg, n = 8, P < 0.05). Forskoli n, an unspecific activator of the adenylate cyclase, caused a signific ant release of somatostatin-like immunoreactivity (10(-6) M: 57.3 +/- 13.2 pg/mg, basal: 30.0 +/- 5.8 pg/mg, n = 13, P < 0.01) which was fur ther augmented in the presence of the phosphodiesterase inhibitor 3-is obutyl-1-methylxanthine (IBMX 10(-4) M) (77.0 +/- 17.8 pg/mg, n = 13, P < 0.01). 3-Isobutyl-1-methylxanthine and N-6,2'-O-dibutyryladenosine -3',5'-cyclic monophosphate mimicked the effect of forskolin and VIP. The release of somatostatin was paralleled by an increase of cAMP immu noreactivity in the presence of VIP (10(-6) M: 37.1 +/- 9.4 pmol/mg, b asal: 19.8 +/- 4.2 pmol/mg, n = 10, P < 0.05), isoproterenol (10(-5) M : 42.4 +/- 9.8 pmol/mg, basal: 16.7 +/- 2.4 pmol/mg, n = 12, P < 0.01) and forskolin (10(-6) M: 47.1 +/- 12.4 pmol/mg, basal: 19.8 +/- 4.2 p mol/mg, n = 10, P < 0.01). The effect of nitric oxide (NO) which acts as an inhibitory neurotransmitter in the enteric nervous system was st udied. NO is known to activate soluble guanylate cyclase to induce tra nsmitter release. The NO-generating compound sodium nitroprusside and bromoguanosine-3',5'-cyclic monophosphate (8-Br-cGMP) had no effect on the release of somatostatin-like immunoreactivity. These data demonst rate the stimulatory effect of VIP, secretin and isoproterenol on rele ase of somatostatin-like immunoreactivity from enteric synaptosomes, w hich is presumably mediated by cAMP-dependent mechanisms. cGMP-depende nt mechanisms seem to be of minor relevance.