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Inhibition by adrenergic neurone blocking agents of the relaxation induced by BRL 38227 in vascular, intestinal and uterine smooth muscle
Author(s) -
Berry J.L.,
Small R.C.,
Hughes S.J.,
Smith R.D.,
Miller A.J.,
Hollingsworth M.,
Edwards G.,
Weston A.H.
Publication year - 1992
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.1476-5381.1992.tb12740.x
Subject(s) - guanethidine , chemistry , endocrinology , bretylium , medicine , prazosin , phenoxybenzamine , phenylephrine , sodium nitroprusside , pharmacology , adrenergic , stimulation , biochemistry , propranolol , receptor , nitric oxide , blood pressure , antagonist
1 The adrenergic neurone blocking agents, guanethidine and bretylium, have been tested for inhibitory activity against the actions of some relaxant drugs (BRL 38227, noradrenaline, sodium nitroprusside, theophylline) in vascular, intestinal and uterine smooth muscle. 2 In guinea‐pig isolated taenia caeci pre‐contracted with KCl (25 m m ), BRL 38227 (0.1–10 μ m ) and noradrenaline (10 n m ‐100 μ m ) each caused concentration‐dependent relaxation. Guanethidine and bretylium (50 μ m ) each antagonized the relaxation to BRL 38227 but not that to noradrenaline. At high concentration (500 μ m ), the adrenergic neurone blocking agents antagonized the action of BRL 38227 and, to some extent, that of noradrenaline. 3 In rat isolated aorta pre‐contracted with noradrenaline (300 n m ), BRL 38227 (0.0125–3.2 μ m ) and sodium nitroprusside (0.3–100 n m ) each produced concentration‐dependent smooth muscle relaxation. Guanethidine and bretylium (5–500 μ m ) each antagonized the action of BRL 38227 without antagonizing that of sodium nitroprusside. 4 Rats were pretreated with 17‐β oestradiol benzoate. Tension waves were then induced from segments of isolated, oestrogen‐dominated uterus by transmural electrical stimulation or by oxytocin (0.2 n m ). These tension waves were inhibited by BRL 38227 (0.025–3.2 μ m ) or theophylline (0.05–0.8 m m ) in a concentration‐dependent manner. Guanethidine (50 μ m ) antagonized the action of BRL 38227 in both the electrically‐ and oxytocin‐driven tissues. In the electrically‐driven tissues, guanethidine (50 μ m ) did not antagonize the inhibition to theophylline. 5 In KCl (25 m m )‐treated guinea‐pig taenia caeci, guanethidine (50 μ m ) inhibited the efflux of 86 Rb + evoked by BRL 38227 (10 μ m ) but not that evoked by noradrenaline (10 μ m ). In contrast, apamin (100 n m ) reduced the efflux of 86 Rb + which was promoted by noradrenaline, but did not affect efflux induced by BRL 38227. 6 It is concluded that the adrenergic neurone blocking agents, guanethidine and bretylium (each at 50 μ m ), selectively inhibit the relaxant action of BRL 38227 in vascular, intestinal and uterine smooth muscle. If this inhibition reflects direct blockade of the K + ‐channel (K KCO ) which is opened by BRL 38227, then the adrenergic neurone blocking agents act as inhibitors selective for K KCO as opposed to the small, apamin‐sensitive (SK Ca ) and large (BK Ca ) conductance, Ca 2+ ‐dependent K + ‐channels.