Characterization of muscarinic receptorsmediating vasodilation in rat perfused kidney

Abstract

The muscarinic receptor mediating vasodilation of resistance vesse]s in the rat iso]ated, constant-pressure perfused kidney vasodilation disappeared after destruction of the endothelium with detergent. Highly significant correlations of agonist potencies for vasodilation were found between rat kidney and guinea-pig ileum submucosal arterioles as weH as agonist potencies at smooth muscle muscarinic M 3 receptors of the guinea-pig ileum. The rank order of antagonist potencies (4-diphenylacetoxy-Nmethylpiperidine methiodide (4-DAMP) > (R)-hexahydro-difenidol -hexahydro-sila-difenidol > pirenzepine -p-fluorohexahydro-sila-difenidol-himbacine-AF-DX 384-AQ-RA 741 > (S)-hexahydro-difenidol) to attenuate vasodilation to APE in rat kidney, correlated significantly with affinities at M 3 receptors in submucosal arterioles and in smooth muscle of the guinea-pig ileum, but differed from those at M 1 and M 2 receptors in rabbit vas deferens. The agonist and antagonist potencies suggest that vasodilation elicited by muscarinic stimuli in endothelium-intact rat renal vasculature is mediated by functional muscarinic M 3 rcceptors.

Nitric oxide‐dependent relaxation induced by M1 muscarinic receptor activation in the rat small intestine

“…This is in agreement with previous data indicating direct M 3 receptormediated intestinal smooth muscle contraction (Eglen et al, 1994). The rank order of potency of telenzepine on muscarinic receptors is M 1 4M 3 4M 2 (Eltze et al, 1993;Waelbroeck, 1992), and for p-F-HHSiD it is M 3 4M 1 4M 2 (Lambrecht et al, 1989). The chosen dose of telenzepine in this study has earlier been shown to successfully inhibit M 1 receptordependent nerve-induced NO-formation from intestinal tissue, without a ecting the M 3 receptor-dependent contractile response (Iversen et al, 1997).…”

“…Our results suggest a neuronal M 1 receptor-dependent NO release while endothelium derived NO release has been associated with muscarinic M 3 receptor activation as evident from studies in di erent vascular tissues (Ren et al, 1993;Eltze et al, 1993). Thus, a reasonable assumption may be that NO formation in di erent tissues is regulated by di erent receptor subtypes.…”

“…Four receptor subtypes have been pharmacologically identi®ed and a ®fth subtype has been genetically identi®ed (Eglen et al, 1994;Hulme et al, 1990). Previously the muscarinic receptor agonist 4- amino]-carbonyl]oxyl-N,N,N-trimethyl-2-butyn-1-amonium chloride , with functional selectivity for muscarinic M 1 receptors (Lambrecht et al, 1993;Micheletti & Schiavone, 1990), has been shown to cause intestinal relaxation in the conscious dog and anaesthetized cat as well as in isolated rat ileium (Carlson et al, 1970;Smith, 1966). McN-A-343 has also been shown to induce relaxation in isolated rat small intestine and inhibition of intestinal motility in conscious dogs via muscarinic M 1 receptor activation.…”

In vitro effects of bethanechol on specimens of intestinal smooth muscle obtained from the duodenum and jejunum of healthy dairy cows

“…The mAChR antagonists used in the study reported here possess differing selectivity for the various mAChR subtypes, depending on their affinity patterns. Thus, the affinity pattern for pirenzepine 47 15,45,50 Affinity data for tropicamide are sparse, but this receptor antagonist appears to bind primarily to M 4 . 51,52 We are not aware of any receptor antagonists with high affinity for M 5 receptors.…”

“…where C is the compound concentration, K is the EC 50 , and α describes the shape of the function (Hill coefficients with values > 1 describe curves with a flat low-dose region and high curvature, whereas values < 1 correspond to curves that increase rapidly). Significance of comparisons made on the basis of this model was determined by use of the likelihood ratio statistic, which yielded a χ 2 test.…”