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Characterization of α 1 ‐adrenoceptors mediating vasoconstriction to noradrenaline and nerve stimulation in the isolated perfused mesentery of rat
Author(s) -
Williams T.J.,
Clarke D.E.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13259.x
Subject(s) - prazosin , stimulation , vasoconstriction , chemistry , endocrinology , medicine , spiperone , perfusion , antagonist , receptor
1 The objective of this study was to investigate the α 1 ‐adrenoceptor subtype(s) mediating vasoconstrictor responses to perfused and neuronally‐released noradrenaline (NA) in the isolated perfused mesentery preparation of rat. 2 Isolated mesenteric preparations (with gut attached) from male Sprague Dawley rats (250–300g) were perfused via the superior mesenteric artery with oxygenated Krebs solution at approximately 6 ml min −1 . The effects of antagonists on vasoconstrictor responses to either perfused (±)‐NA or periarterial nerve stimulation (70 V, 2 ms pulse width, 10 s train) were determined. 3 Vasoconstrictor responses to perfused NA were antagonized by prazosin (pA 2 = 9.3 ± 0.1), WB4101 (pA 2 = 9.6 ± 0.1), 5‐methyl urapidil (5‐MU: pA 2 = 9.0 ± 0.1), (+)‐niguldipine (insurmountable) and spiperone (pA 2 = 7.7 ± 0.1). The insurmountable nature of the antagonism by (+)‐niguldipine (0.1 n m ) was greatly reduced by co‐perfusion with prazosin (10 n m ). Chloroethylclonidine (CEC: 100 μ m for 20 min, followed by 40 min washout) caused an approximate twofold increase in the EC 50 for (±)‐NA and reduced the maximum response by approximately 25%. Pre‐treatment of tissues with CEC (100 μ m as above) did not significantly alter affinity estimates for prazosin (pA 2 = 9.2 ± 0.1), WB4101 (pA 2 = 9.3 ± 0.1) or 5‐MU (pA 2 = 8.7 ± 0.2). Vasoconstrictor responses to periarterial nerve stimulation were antagonized by WB4101>5‐MU>prazosin ≫ spiperone. CEC (100 μ m as above) reduced nerve‐stimulated responses by approximately 50%. 4 The affinity estimates for the various antagonists studied suggest that vasoconstrictor responses to both exogenous and neuronally‐released NA are mediated via the same α 1 ‐adrenoceptor subtype. The pharmacological profile most resembles the ‘classical’ α 1A ‐adrenoceptor, which, in turn, appears to be a rat homologue of the cloned bovine α 1C ‐adrenoceptor.