Details

Autor(en) / Beteiligte

• Bungardt, Edwin
• Vockert, Elisabeth
• Feifel, Roland
• Moser, Ulrich
• Tacke, Reinhold
• Mutschler, Ernst
• Lambrecht, Günter
• Surprenant, Annmarie

Titel

Characterization of muscarinic receptors mediating vasodilation in guinea-pig ileum submucosal arterioles by the use of computer-assisted videomicroscopy

Ist Teil von

• European journal of pharmacology, 1992-03, Vol.213 (1), p.53-61

Ort / Verlag

Amsterdam: Elsevier B.V

Erscheinungsjahr

1992

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• Muscarinic receptors of resistance vessels (submucosal arterioles, outside diameter 50–75 μm) from the guinea-pig small intestine were investigated in vitro using a computer-assisted videomicroscopy system (Diamtrak®). The muscarinic receptor which mediates vasodilation of precontracted [U-46619 (300 nM) or (−)-noradrenaline (10 μM)] arterioles was characterized with several muscarinic agonists and subtype-selective antagonists. The following agonists all produced equivalent maximum vasodilation (given in rank order of potency): acetylcholine = arecaidine propargyl ester (APE) > oxotremorine = (±)-muscarine = (±)-methacholine > carbachol > 4-[[N-(4-chlorophenyl)carbamoyl]oxy]-2- butynyltrimethylammonium iodide (4-Cl-McN-A-343). 4-[[N-(3-Chlorophenyl)-carbamoyl]oxy]-2-butynyltrimethylammonium chloride (McN-A-343) and N-ethyl-guvacine propargyl ester (NEN-APE) produced minimal or no arteriolar vasodilation. The muscarinic antagonists pirenzepine, (±)-5,11-dihydro-11-[[[2-[2-((dipropylamino)methyl)-1-piperidinyl]ethyl]amino]-carbonyl]-6H-pyrido(2,3-b)(1,4)-benzodiazepin-6-one (AF-DX 384), 11-[[4-[4-(diethylamino)butyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido(2,3-b)(1,4)-benzodiazepin-6-one (AQ-RA 741), p-fluorohexahydro-sila-difenidol (p-F-HHSiD), 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and (R)- and (S)-hexahydro-difenidol [(R)-HHD, (S)-HHD] shifted the muscarine, methacholine or carbachol dose-response curve to the right in a competitive manner. Schild analysis of the data yielded pA 2 values for pirenzepine (6.74/6.9), AF-DX 384 (6.72), AQ-RA 741 (6.58), p-F-HHSiD (7.53/7.57), 4-DAMP (9.06), (R)-HHD (7.88/8.32) and (S)-HHD (5.52/5.88). Thus, it can be concluded that submucosal arterioles possess only the M 3 functional muscarinic receptor, the activation of which causes blood vessel dilation. The preparation described is considered to be a valuable new bioassay for pharmacological investigations of drug actions at muscarinic receptors in the peripheral vascular system.