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A61603‐Induced Contractions of the Porcine Meningeal Artery Are Mediated by α 1 ‐ and α 2 ‐Adrenoceptors
Author(s) -
Mehrotra Suneet,
Gupta Saurabh,
Centurión David,
Villalón Carlos M.,
Saxena Pramod R.,
VandenBrink Antoinette Maassen
Publication year - 2007
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2007.00050.x
Subject(s) - rauwolscine , prazosin , yohimbine , methoxamine , phenylephrine , endocrinology , medicine , agonist , pharmacology , chemistry , antagonist , alpha (finance) , receptor , blood pressure , construct validity , nursing , patient satisfaction
It has recently been shown that A61603 (N‐[5‐(4,5‐dihydro‐1H‐imidazol‐2yl)‐2‐hydroxy‐5,6,7,8‐tetrahydro‐naphthalen‐1‐yl]methane sulphonamide), a potent α 1A ‐adrenoceptor agonist, decreased carotid artery conductance in anaesthetized pigs by a novel non‐adrenergic mechanism. In this study, we set out to pharmacologically characterize A61603‐induced contractions of the porcine isolated meningeal artery. While the maximum contractile responses of the artery were similar, A61603 (E max : 183 ± 23% of 100 mM KCl; pEC 50 : 7.25 ± 0.18) was more potent than noradrenaline (E max : 156 ± 16%; pEC 50 : 5.75 ± 0.17) or phenylephrine (E max : 163 ± 20%; pEC 50 : 5.63 ± 0.02). Prazosin (pA 2 : 9.36 ± 0.23) and, to a lesser extent, rauwolscine (pK b : 6.36 ± 0.38) and yohimbine (pK b : 7.30 ± 0.15) antagonised the contractions to A61603. The 5‐HT 1B (GR127935; N‐[4‐methoxy‐3‐(4‐methyl‐1‐piperazinyl) phenyl]‐2′‐methyl‐4′‐(5‐methyl‐1,2,4‐oxadiazol‐3‐yl)[1,1‐biphenyl]‐4‐carboxamide) and 5‐HT 2 (ritanserin) receptor antagonists failed to affect the responses to A61603, but methiothepin, which, in addition, has a high affinity for α‐adrenoceptors, proved an effective antagonist. The A61603‐induced responses were suppressed by the cAMP stimulator forskolin, but not by the protein kinase C inhibitor chelerythrine. Our results suggest that the contraction of porcine isolated meningeal artery by A61603 is mediated via mainly α 1 ‐(probably α 1A ) and, to a lesser extent, α 2 ‐adrenoceptors, involving the adenylyl cyclase, but not the diacylglycerol pathway.