ISSN:
1432-1912
Schlagwort(e):
Key words Rat anococcygeus muscle
;
Muscarinic
;
receptor subtypes
;
Muscarinic agonists
;
Muscarinic
;
antagonists
;
M3 receptors
;
Stereoselectivity
;
Hexahydro-difenidol
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Abstract The present study was designed to characterize the postjunctional muscarinic receptors mediating contraction in rat anococcygeus muscle by means of a series of muscarinic agonists and subtype-preferring key muscarinic antagonists. Cumulative addition of muscarinic agonists elicited concentration-dependent contractions with the following rank order of potency (pD2 values): (+)-muscarine (6.36) ≥ oxotremorine M (6.21) ≥ arecaidine propargyl ester (APE) (6.18) 〉 carbachol (5.68)=(±)-methacholine (5.65) 〉 4-(4-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium chloride (4-Cl-McN-A-343) (4.28) 〉 4-(3-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343) (3.89). (+)-Muscarine, oxotremorine M, carbachol and (±)-methacholine behaved as full agonists, whereas APE, 4-Cl-McN-A-343 and McN-A-343 displayed partial agonism. The contractile responses of the rat anococcygeus muscle to (±)-methacholine were competitively antagonized by pirenzepine (pA2=6.92), 11-[[4-[4-(diethylamino)butyl]-1-piperidinyl]acetyl] 5,11-dihydro-6H-pyrido(2,3-b)(1,4)-benzodiazepine-6-one (AQ-RA 741; pA2=6.75), himbacine (pA2=7.11), (±)-p-fluoro-hexahydro-sila-difenidol (p-F-HHSiD; pA2=7.68) and the (R)- and (S)-enantiomers of hexahydro-difenidol [(R)-HHD: pA2=8.52; (S)-HHD: pA2=6.06]. A comparison of the pA2 values derived from studies of contraction in rat anococcygeus muscle with literature binding (pKi values) and functional affinities (pA2 values) obtained at native M1-M4 receptors strongly suggests that the postjunctional muscarinic receptors mediating contraction in rat anococcygeus muscle are of the M3 subtype.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/PL00005104
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