Differential action of somatostatin on peptide-induced release of acetylcholine.
In this study we examine the mechanism by which somatostatin (SRIF-14) inhibits cholecystokinin octapeptide- (CCK-8) but not substance P-mediated release of [3H]acetylcholine (ACh) from the guinea pig ileum. 2',5'-Dideoxyadenosine, an inhibitor of adenylate cyclase, antagonized the action of CCK-8 and forskolin but had no effect on substance-P-evoked release of [3H]ACh. Addition of theophylline enhanced the release of [3H]ACh stimulated by CCK-8 but not by substance P. These observations suggest that CCK-8, but not substance P, can stimulate cholinergic transmission via an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent pathway. Somatostatin inhibited release of [3H]ACh evoked by CCK-8 and forskolin in a dose-related manner. CCK-8- and forskolin- but not substance P-evoked release of [3H]ACh were maximally inhibited in the presence of 10(-6) M somatostatin (49 +/- 5 and 48 +/- 7% of control, respectively). Pretreatment with pertussis toxin (inactivates inhibitory guanine nucleotide binding proteins) reversed the inhibitory effect of somatostatin on the release of [3H]ACh evoked by CCK-8. These observations suggest that CCK-8 but not substance P can stimulate [3H]ACh by a cAMP-dependent pathway. Somatostatin appears to inhibit the cAMP-dependent component of CCK-8-mediated cholinergic transmission via activation of a pertussis toxin-sensitive G protein.
Kowal
V
V
Department of Internal Medicine, University of Michigan, Ann Arbor 48109.
Wiley
J W
JW
Owyang
C
C
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D037361:Adenylate Cyclase Toxin; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D015224:Dideoxynucleosides / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D009197:Myenteric Plexus / Q000502:physiology; D037342:Pertussis Toxin; D012844:Sincalide / Q000494:pharmacology*; D013004:Somatostatin / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology*; D013806:Theophylline / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D015224:Dideoxynucleosides; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013373:Substance P; D016048:Dideoxyadenosine; D013004:Somatostatin; C021008:2',5'-dideoxyadenosine; D013806:Theophylline; D000242:Cyclic AMP; D037342:Pertussis Toxin; D012844:Sincalide; D000109:Acetylcholine