Inhibition of endogenous acetylcholine release by blockade of voltage-dependent calcium channels in enteric neurons of the guinea-pig colon.
The effects on acetylcholine release from the guinea-pig colon of the N-type calcium channel blocker omega-conotoxin GVIA (omega-conotoxin), the L-type calcium channel blocker nifedipine and the putative blocker of T-type channels, flunarizine, have been investigated. Endogenous basal acetylcholine release and electrically (1 Hz, 1 ms, 450 mA)-evoked overflow in the presence of cholinesterase inhibitor were studied. omega-Conotoxin (1-10 nM) and nifedipine (0.03-3 microM) dose-dependently inhibited basal and electrically-evoked acetylcholine release. Maximal inhibition of basal or electrically-evoked acetylcholine release was about 40% for nifedipine and about 75% for omega-conotoxin. The potency of nifedipine was inversely related to the external calcium concentration: its EC50 value in low-calcium medium (0.5 mM) was as low as 12 nM. Flunarizine inhibited acetylcholine release only at concentrations higher than 0.2 microM. Our results are consistent with an involvement of N- and L-type calcium channels in the control of the endogenous acetylcholine release from the guinea-pig colon.
Marino
F
F
University of Pavia, 2nd Faculty of Medicine, Department of Internal Medicine and Therapeutics, Varese, Italy.
Marcoli
M
M
De Ponti
F
F
Lecchini
S
S
Castelletti
C M
CM
Frigo
G M
GM
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D004558:Electric Stimulation; D004594:Electrophysiology; D005444:Flunarizine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010456:Peptides, Cyclic; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D000109:Acetylcholine; D005444:Flunarizine; D002118:Calcium