Pharmaco‐mechanical coupling in the response to acetylcholine and substance P in the smooth muscle of the rat iris sphincter

Banno, Hitoshi; Imaizumi, Yuji; Watanabe, Motoi

doi:10.1111/j.1476-5381.1985.tb11090.x

Cited by 25 publications

(10 citation statements)

References 24 publications

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“…Phone : 052-836-3431 Fax : 052-836-3431 e-mail:mwatanab@phar.nagoya-cu.ac.jp Shimizu, 1982Kessler, 1985. The parasympathetic transmission in the muscle is characteris tic of its electrical features, since the contraction induced by acetylcholine, which is released from nerve endings or added externally, is triggered by neither depolarization nor action potential in sphincter smooth muscle cells (Banno et al, 1985, Imaizumi et al, 1984. This indicates that the transmission is mediated by a typical pharmaco-mechanical coupling (Som lyo et al .…”

Section: Introductionmentioning

confidence: 99%

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

Tanaka¹,

Yamahara²,

Kondoh³

et al. 1999

J. Smooth Muscle Res.

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Effects of ethylcholine mustard aziridinium ion (AF64A) on contractile responses to agonists or transmural nerve stimulation (TNS) were examined in rat iris sphincter muscle.The responses to TNS of isolated sphincter muscle were abolished within 1 hr after the addition of 0.1 mM AF64A to the bathing solution, while responses to acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) were not changed significantly. In sphincter muscles which were isolated 3 days after the micro-injection of 100 nmol AF64A into the anterior chamber of eyes in vivo, the response to TNS were decreased to about 30% of the control.The injection of AF64A at higher concentrations often resulted in serious chronic damage of the eye. When 100 nmol AF64A was injected twice with an interval of 3 days, the response to TNS was decreased to about 20% of the control. Maximum responses and sensitivities to ACh and 5-HT were markedly enhanced in sphincters from eyes which had been treated with AF64A twice. The sensitivity of depolarized sphincters to external Ca2+ was also increased significantly. Seven weeks after the second injection, responses to TNS recover ed to more than 50% of the control and the effects of AF64A mostly disappeared. In conclusion, the acute inhibition of parasympathetic transmission without postsynaptic changes can be achieved within 1 hr after bath-application of 0.1 mM AF64A. The reduc tion of parasympathetic nerve activity by treatment with AF64A in vivo induces nonspecific supersensitivity in iris sphincter, whereas effects of AF64A were mostly reversible under the present experimental conditions.

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Section: Introductionmentioning

confidence: 99%

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

Tanaka¹,

Yamahara²,

Kondoh³

et al. 1999

J. Smooth Muscle Res.

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“…Recently, mechanical (16) and electrical responses (17,18) to some agonists have been investigated in isolated rat iris sphincter and dilator muscles. In the present study, characteristics of the supersensitivity caused by ciliary ganglionectomy of the rat iris sphincter were investigated using acetyl choline (ACh), bethanechol (BeCh), serotonin (5-HT) and K+ as agonists.…”

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confidence: 99%

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

1987

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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.

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“…Partial membrane depolarization has been described in various tissues sensitized by denervation or drug-treatment (guinea-pig vas deferens (12), rat portal vein (11 ), rabbit saphenous artery (28)) and was considered to play an important role in the development of postjunctional supersensitivity. As we have previously reported, ACh contracts the muscle exclusively through nonelectrical activation (pharmaco-mechanical coupling: PMC) in normal rat iris (15). Therefore, the small depolarization induced by ACh (>10 ItM) might account for the supersensitivity to ACh; an additional Ca influx via voltage sensitive Ca-channels which occurs during the depolarization contributes to an increase in tension.…”

Section: Methodsmentioning

confidence: 84%

“…larger than the symbol . produced a dose-dependent contraction without modifying the membrane potential in the rat iris sphincter (15). Therefore, we examined the possibility that the membrane depolarizes in response to ACh in the denervated muscle.…”

Section: Methodsmentioning

confidence: 99%

“…There is, however, no extensive study on the mechanisms of nonspecific supersensitivity after cholinergic denervation. We have previously reported that acetyl choline (ACh) contracts rat iris sphincter muscle without significant change in the membrane potential under normal conditions (typical of pharmaco-mechanical coupling: PMC), while potassium ions contract the muscle by causing depolarization (typical of EMC) (15). In this muscle, an extensive postjunctional supersensitivity develops to ACh as well as to potassium ions (K) following denervation (4).…”

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Cellular mechanisms of supersensitivity to acetylcholine and potassium ion after ciliary ganglionectomy in the rat iris sphincter muscle.

1987

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Abstract-The effect of parasympathectomy on the electrical and nonelectrical activation of iris smooth muscle cells was examined 7-10 days after ciliary gan glionectomy in order to explore the mechanisms involved in the nonspecific dener vation supersensitivity. Resting membrane potential of rat iris sphincter muscle cells was not altered by cholinergic denervation. Although the degree of depolari zation induced by raising [K]o was little affected by denervation, K-contracture was always potentiated. Acetylcholine (ACh) never modified membrane potential in normal iris muscles even at a high concentration of 50 iiM. After denervation, ACh produced a much larger contraction, and at higher concentrations, concomitantly produced a depolarization which was far too small to account for the enhanced contraction. There were 3 and 4.6-fold increases in sensitivity to Ca and Sr, respectively, in the contractile response in high-K, Ca-free solution after denervation. The response to Ca was greatly enhanced also in height, and a large part of the increment of the response to 2 mM Ca was suppressed by 0.1 W nifedipine. In the depolarized muscle of normal irides, Mn ion had two distinct effects, a calcium blocking effect at lower concentrations (<1.2 mM) and a contractile effect at higher concentrations (> 1 .8 mM). Denervation caused a marked increase in the contractile effect of Mn (>0.6 mM). ACh elicited phasic contraction only once in the absence of external Ca. This response was much enhanced by parasympa thectomy. Fluoride ion (F) also produced a distinct contraction many times in the Ca-free solution. F-induced contraction was much larger in denervated muscle than in normal muscle. These results i) indicate that denervation of the rat iris sphincter muscle does not significantly affect the electrical property of the muscle cells, ii) and suggest that denervation may increase Ca-influx of the cell membrane, iii) may increase the amount of releasable Ca from an intracellular store site, and iv) might increase the functional activity of the contractile protein.

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Pharmaco‐mechanical coupling in the response to acetylcholine and substance P in the smooth muscle of the rat iris sphincter

Cited by 25 publications

References 24 publications

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

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

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

Cellular mechanisms of supersensitivity to acetylcholine and potassium ion after ciliary ganglionectomy in the rat iris sphincter muscle.

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