PHARMACO-MECHANICAL COUPLING IN THE RESPONSE TO ACETYLCHOLINE AND SUBSTANCE-P IN THE SMOOTH-MUSCLE OF THE RAT IRIS SPHINCTER

In the rat iris sphincter muscle contractile responses to transmural stimulation consisted of 2 components, a fast cholinergic followed by a slow non-adrenergic, non-cholinergic (NANC) one. The magnitude of the latter varied widely and was on average 5% of that of the cholinergic component. Exogenous substance P (1 nM-1 mM) produced a concentration-dependent contraction, the maximum amplitude of which was as large as that produced by acetylcholine (ACh). Capsaicin (10 .mu.M) induced a transient contraction only once in each preparation. After the treatment with capsaicin the NANC component disappeared. Neither nerve nor direct electrical stimulation with short pulses elicited any active change in the membrane potential under physiological conditions, but an action potential was triggered by direct stimulation when the extracellular Ca2+ was totally replaced by Ba2+. Under the latter conditions spontaneous spike potentials occurred repetitively. ACh and substance P produced a large contraction without modifying the membrane potential. This was also the case in the presence of 5 mM Ba. Substance P-ergic innervation may have a far lesser physiological significance than that which has been described in rabbits and pure pharmacomechanical coupling is characteristic of the responses to ACh, substance P and nerve stimulation in the rat iris sphincter muscle.