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

Abstract

Abstract-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 para sympathetically denervated. We used rats because the denervation supersensi tivity 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 re sponses 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 dener vation 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.

Supersensitivity by AF64A, a Novel Inhibitor of Neuronal Choline-Uptake, of the Rat Iris Sphincter Smooth Muscle.

“…It is notable that not only the maximum response to high K+ but also the sensitivity to extracellular Ca2+ was markedly increased. These are exactly the same as the results obtained by parasympathetic denervation by ciliary ganglionectomy (Hasegawa et al ., 1987). The mechanisms, however, underlying the nonspecific supersensitivity by the AF64A injection were not further examined in the present study .…”

“…An increase in the sensitivity of the contractile proteins by a change in the activity or amount of calmodulin has been proposed to explain the supersensitivity induced by the sympathetic denervation (Ramos et al, 1986). Similar possibility has been suggested in parasympathectomized iris sphincter or dilator (Hasegawa et al, 1987Banno et al, 1987Hashimoto et al, 1993. Further experiments are required , especially using skinning tech niques, to elucidate the mechanisms for AF64A-induced nonspecific supersensitivity.…”

“…Since most of parasympathetic ganglia are located in the target organs, the surgical denervation is not practical except for a few organs. Surgical parasympathetic denervation of iris smooth muscle can be performed by ciliary ganglionectomy and results in solution), respectively, in the sphincter (Hasegawa et al, 1987 ;Banno et al, 1987) or the dilator (Hasegawa et al, 1988 ;Hashimoto et al, 1993). The chemical sympathetic denervation using 6-hydroxydopamine (Kostrzewa and Jacobowitz, 1975) or guanethidine (Burnstock et al, 1971 ;Shibata et al, 1989) and the depletion of noradrenaline in sympathetic nerve endings using reserpine (Trendelenburg and Gravenstein, 1958 ;Zaimis, 1961) have been giving advantages to clarify neuronal controls of tissue functions by both central and peripheral sympathetic nerves.…”

Characterization of muscarinic receptors mediating relaxation and contraction in the rat iris dilator muscle

“…At the start of the experiment, resting tone was adjusted to 10 mg and 50 mg in the dilator and sphincter muscles, respectively. Marmfors & Nilsson (1964) as modified by Hasegawa et al (1987) and Hashimoto et al (1993). Since the changes in drug-sensitivity reached steady levels about 2 to 3 days after ciliary ganglionectomy, the denervated dilator muscles were used in experiments 1 week after the operation (Hasegawa et al, 1988).…”

Mechanism of action of nicotine in isolated iris sphincter preparations of rabbit

“…In the present study, we investigated the mechanism of action of nicotine in an isolated iris sphincter preparation of rabbit, which, exceptionally, is densely innervated by parasympathetic neurones and free of ganglia (Schaeppi, 1966;Hasegawa et al, 1987). Since it has recently been reported that there are capsaicin-sensitive primary sensory neurones in isolated preparations (Ueda et al, 1981;, the effect of nicotine on the sensory nerve terminals was also studied.…”