Stimulation of acetylcholine release in myenteric plexus by calcitonin gene-related peptide.
The effects of calcitonin gene-related peptide (CGRP) on acetylcholine (ACh) release from myenteric plexus neurons in primary culture were investigated. CGRP (10(-12) to 10(-6) M) produced a dose-dependent increase in [3H]ACh release. The ACh release caused by CGRP was significantly inhibited (74 +/- 24%) by preincubation with dideoxyadenosine but was increased more than threefold by preincubation with theophylline. Incubation of myenteric plexus neurons with CGRP (10(-8) M) in the presence of diltiazem (10(-5) M) or in a calcium-free medium markedly reduced [3H]ACh release. CGRP potentiated [3H]ACh release stimulated by potassium or substance P but not by cholecystokinin octapeptide or forskolin. The results demonstrate that CGRP cause release of ACh from guinea pig myenteric plexus neurons and suggest that the peptide acts through an adenosine 3',5'-cyclic monophosphate-dependent mechanism that involves neuronal calcium channels.
Mulholland
M W
MW
Department of Surgery, University of Michigan, Ann Arbor 48109-0331.
Jaffer
S
S
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D012844:Sincalide / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D005576:Colforsin; D013373:Substance P; D016048:Dideoxyadenosine; D013806:Theophylline; D004110:Diltiazem; D015740:Calcitonin Gene-Related Peptide; D012844:Sincalide; D000109:Acetylcholine