Parasympathetic denervation supersensitivity in the rat iris sphincter muscle: an in vitro study

Supersensitivity in chronically sympathectomized smooth muscle has long been studied, but little is known about chronically parasympathectomized smooth muscles. Iris is one of the few smooth muscle organs which can be parasympathetically denervated. We used rats because the denervation supersensitivity in the vas deferens has extensively been studied in this species. The rat was unilaterally ciliary-ganglionectomized. After 1-13 days, strips of the iris sphincter muscle obtained from denervated eye were tested for the sensitivity to acetylcholine (ACh), 5-hydroxytryptamine (5-HT) and K+. A significant increase in sensitivity to ACh and 5-HT was recognized as early as 1 day after the operation, and the sensitivity reached a maximum after 5-6 days, when ED50 values of ACh and 5-HT were reduced to approximately 1/28 and 1/4, respectively. The sensitivity to K+ was unaffected. When the sensitivity reached the maximum, the maximum responses to ACh, 5-HT and K+ were increased by 50%, 140% and 50%, respectively. The shift of the dose-response curve for bethanechol (BeCh) after denervation was comparable to that for ACh. Physostigmine shifted the curve for ACh, but did not shift that for BeCh either before or after denervation. Specific binding of 3H-quinuclidinyl benzylate tended to decrease after denervation, but the change was statistically not significant. These results indicate that the parasympathetic denervation supersensitivity in the rat iris sphincter involves a non-specific component, in addition to one specific to ACh and BeCh. The specific component seems to involve postsynaptic mechanisms.