M2 muscarinic receptors on the iris sphincter muscle differ from those on iris noradrenergic nerves

Bognar, Irene T.; Baumann, Barbara; Dammann, Florian; Knöll, Beate; Meincke, M.; Pallas, Sylvia; Fuder, H.

doi:10.1016/0014-2999(89)90195-7

Cited by 34 publications

(18 citation statements)

References 28 publications

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“…The present study revealed that the ACh-induced inhibition of the pressor response to adrenergic nerve stimulation was not altered by the addition of pirenzepine at 10-g M, a concentration sufficient to selectively inhibit M1 receptor subtype (16,20) or by 10-9 M 4-DAMP, which is enough to selectively block M3 subtype (21-23). It has been reported that pA2 values for AF-DX 116 at M2 receptors range from 6.8 to 7.4 (6,11,12). The present study demonstrated that the inhibition by ACh of the pressor response to adrenergic nerve stimulation was significantly reversed by AF-DX 116 in concentrations of 10-~ M or higher, suggesting that the prejunctional muscarinic receptor subtype involved is M2.…”

Section: Discussionsupporting

confidence: 58%

“…Modulatory prejunctional muscarinic receptors are present on neurons liberating various neurotransmitters, and there is evidence that the subtypes of muscarinic receptors involved at these sites are not identical for all neurons. The prejunctional muscarinic inhibitory heteroreceptors present on sympathetic nerves in different tissues also vary as to their subtype; those in the heart (9-11) and rabbit iris (12) appear to be muscarine M2 receptors, whereas those in the rabbit vas deferens are of the M1 subtype (13). Nevertheless, little is known about the subtype of these receptors present on adrenergic nerve endings modulating norepinephrine release in dog mesenteric arteries.…”

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confidence: 96%

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Prejunctional Regulation by Endogenous and Exogenous Acetylcholine of Adrenergic Nerve Function in Isolated Canine Mesenteric Arteries.

1997

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Transmural electrical stimulation (5-30 Hz) produced a frequency-dependent increase in the perfusion pressure of isolated, perfused dog mesenteric artery segments without the endothelium, which was abolished by prazosin or tetrodotoxin. Physostigmine inhibited the pressor response to transmural electrical stimulation, whereas atropine potentiated the response. Treatment with acetylcholine (10-6 and 10-5 M) dose-dependently inhibited the response to electrical nerve stimulation. The effect was reversed by the addition of atropine and AF-DX 116 at a concentration (10-~ M) that selectively blocked the M2 receptor subtype, but not by pirenzepine or 4-DAMP. Acetylcholine did not alter the pressure raised by norepinephrine in perfused arterial segments nor the contraction caused by exogenous norepinephrine in the artery strips. 3H-overflow evoked by transmural electrical stimulation from tissues prelabeled with [3H] norepinephrine was decreased by acetylcholine (10-6 M) in the superfused dog mesenteric arterial strips. It is concluded that acetylcholine inhibits adrenergic neurogenic contractions by interfering with the release of norepinephrine, which possibly results from activation of the prejunctional M2 receptor subtype. (Hypertens Res 1997; 20: 119-125)

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Section: Discussionsupporting

confidence: 58%

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confidence: 96%

Prejunctional Regulation by Endogenous and Exogenous Acetylcholine of Adrenergic Nerve Function in Isolated Canine Mesenteric Arteries.

1997

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“…It has been demonstrated that the activation of these receptors inhibits the activity of adenylyl cyclase via the activation of an inhibitory GTPbinding protein (Gi) [4]. Furthermore, M2 muscarinic receptors have been identified in rabbit and human iris [1,3,6]. Assuming that low tonic release of ACh results in continuous activation of the Gi-adenylyl cyclase pathway, blocking the M2/M4 receptors with atropine or IPB would abolish the inhibition of adenylyl cyclase and result in greater accumulation of cAMP in response to lower doses of β-adrenergic agonists.…”

Section: Discussionmentioning

confidence: 99%

Muscarinic blockers potentiate β-adrenergic relaxation of bovine iris sphincter

Barilan

Nachman-Rubinstein

Oron

et al. 2003

Graefe's Arch Clin Exp Ophthalmol

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“…The muscarinic receptor subtype predominant in iris sphincter muscles of the guinea-pig (Bognar et al, 1990) and the rabbit has been pharmacologically characterized as the M3 type by use of antagonists, whereas the presynaptic muscarinic receptors involved in autoinhibition of ACh release from nerve endings are the M2 type (Bognar et al, 1989). The finding that pilocarpine and McN-A-343, which do not activate phospholipase C (Leiber et at., 1990;Eglen et al, 1993), did not elicit contraction in sphincter muscles or in dilator muscles suggests that the receptor subtype mediating contraction may be common in dilator and sphincter muscles of the rat.…”

Section: Discussionmentioning

confidence: 99%

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

Masuda

Yamahara

Tanaka

et al. 1995

British J Pharmacology

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1 The characteristics of muscarinic receptors mediating relaxation and/or contraction in the rat iris dilator muscle were examined. 2 Relaxation was induced in a dilator muscle by application of acetylcholine (ACh) at low doses (3 gM or less) and contraction was induced by high doses. Methacholine and carbachol also showed biphasic effects similar to those of ACh; in contrast, bethanechol, arecoline, pilocarpine and McN-A-343 induced mainly relaxation but no substantial contraction. 3 After parasympathetic denervation by ciliary ganglionectomy, the relaxant response to muscarinic agonists disappeared upon nerve stimulation. Application of McN-A-343 and pilocarpine induced only small contractions in denervated dilator muscles, indicating that these are partial agonists for contraction.4 pA2 values of pirenzepine, methoctramine, AF-DX 116, himbacine, and 4-DAMP for antagonism to pilocarpine-induced relaxation in normal dilator muscles and those for antagonism to ACh-induced contraction in denervated dilator muscles were determined. The pA2 values for antagonism to relaxation of all these antagonists were most similar to those for M3-type muscarinic receptors. 5 Although pA2 values for contraction of these antagonists, except for methoctramine, were very close to those for relaxation, contraction was not significantly antagonized by methoctramine. Contraction might be mediated by M3-like receptors which have a very low affinity for methoctramine. 6 In conclusion, ACh-induced biphasic responses in rat iris dilator muscles were clearly distinguished from each other by specific muscarinic agonists and parasympathetic denervation, whereas muscarinic receptors could not be subclassified according to the pA2 values of 5 specific antagonists only.

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M2 muscarinic receptors on the iris sphincter muscle differ from those on iris noradrenergic nerves

Cited by 34 publications

References 28 publications

Prejunctional Regulation by Endogenous and Exogenous Acetylcholine of Adrenergic Nerve Function in Isolated Canine Mesenteric Arteries.

Prejunctional Regulation by Endogenous and Exogenous Acetylcholine of Adrenergic Nerve Function in Isolated Canine Mesenteric Arteries.

Muscarinic blockers potentiate β-adrenergic relaxation of bovine iris sphincter

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

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