Modulation of the release of noradrenaline and of noncholinergic, nonadrenergic inhibitory neurotransmitter through presynaptic N-cholinergic receptors by means of depolarizing agents in cat internal anal sphincter.

The contractile activity of smooth-muscle strips (15 X 2 mm), isolated from the internal anal sphincter [IAS] of chloralose-anaesthesized cats, was recorded under isometric conditions. The relaxation effects of exogenously applied acetylcholine (Ach) and nicotine (Ns on cat IAS turn into contractile after treatment of the preparations with depolarizing agent (increased [K+]0 scorpion venom, ouabaine). These contractile effects are blocked completely by phentolamine, guanetidine, hexamethonium and they are antagonized by TTX. Relatively high N concentrations induce a three-phase effect whose second contractile component is phentolamine- and guanethidine-sensitive. Field electrical stimulation (FES - 0.7-20 Hz, 0.1 ms, 40 V, duration 15 s) induces biphasic response in IAS: initial contraction which increases after an increase in [K+]0 and is blocked by phentolamine and guanethidine, with subsequent relaxation which is not affected by adrenergic and cholinergic blockers. The effects of FES are TTX-sensitive. The article discusses the problem of the release of noncholinergic nonadrenergic inhibitory neurotransmitter and of noradrenaline by means of presynaptic N-cholinergic receptors. It is assumed that the correlation in which the two transmitters are released depends on the different threshold value of the membrane potential of the nerve terminals, whereby excitatory-secretion coupling takes place.