Acetylcholine and carbachol prevent muscle depolarization in denervated rat diaphragm.
Muscle fibres of the rat diaphragm kept in a tissue culture medium became depolarized by 8-10 mV within 3 h after denervation. In the presence of carbachol (CB; 5 x 10(-8) M), and acetylcholine (ACh; 5 x 10(-8) M, the post-denervation depolarization was reduced. Both drugs were used in concentrations which mimicked the effect of non-quantal release of ACh. (+)Tubocurarine (TC) and ouabain did not prevent the protective action of CB, indicating that this effect is not mediated through ACh nicotinic receptors or the electrogenic Na+, K+ pump. Addition of Mg2+, verapamil, diltiazem, nifedipine and Cd2+ in concentrations which block Ca2+ entry virtually inhibited the effect of both cholinomimetics. L-Nitroarginine methylester (NAME), an inhibitor of NO synthase, and haemoglobin, an extracellular scavenger of the NO radical, completely eliminated the protective effect of CB on post-denervation depolarization. The retrograde action of NO produced by cholinomimetics on nerve terminals is postulated.
Urazaev
A K
AK
State Medical University, Kazan, Russia.
Naumenko
N V
NV
Poletayev
G I
GI
Nikolsky
E E
EE
Vyskocil
F
F
D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D003714:Denervation; D003964:Diaphragm / Q000187:drug effects* / Q000294:innervation; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002217:Carbachol; D000109:Acetylcholine