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The effect of relaxants working through different transduction mechanisms on the tonic contraction produced in rat aorta by 4β‐phorbol dibutyrate
Author(s) -
Obianime A.W.,
Dale M. Maureen
Publication year - 1989
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.1476-5381.1989.tb12000.x
Subject(s) - methoxamine , cromakalim , forskolin , sodium nitroprusside , isoprenaline , contraction (grammar) , medicine , endocrinology , phorbol , chemistry , protein kinase c , activator (genetics) , agonist , biology , nitric oxide , biochemistry , signal transduction , receptor , stimulation
1 We have examined the effects of a range of smooth muscle relaxants on the maintained contractions produced in rat aortic rings by the protein kinase C activator, 4β‐phorbol dibutyrate; these effects were compared with those on the contraction induced by the selective α 1 ‐adrenoceptor agonist, methoxamine. The phorbol ester, at 0.3 μ m , gave a sustained contraction which was, on average, of approximately the same magnitude as the maximum contraction produced by methoxamine, 10 μ m . 2 The β‐adrenoceptor agonist, isoprenaline (0.01–1 μ m ) caused a dose‐related relaxation of the methoxamine‐induced contraction but had no effect on the contraction induced by the phorbol ester. 3 An activator of adenylate cyclase, forskolin (0.01–1 μ m ) produced a dose‐related relaxation of the methoxamine‐induced contraction and at 0.01–10 μ m caused relaxation of the contraction induced by the phorbol ester. Similar results were obtained with the potassium channel activator, cromakalim (0.001–10 μ m ). 4 An activator of guanylate cyclase, sodium nitroprusside (0.001–100 μ m ) caused a dose‐related relaxation of both the methoxamine‐induced and the phorbol ester‐induced contraction, being more effective on the former than on the latter. Similar results were obtained with enprofylline (11000 μ m ). 5 Methoxamine (10 nM‐100 μ m ), given cumulatively, caused a dose‐related contractile response. Pretreatment with isoprenaline (1 μ m ), enprofylline (10 μ m ) and nicorandil (1 μ m ) resulted in partial decrease of the subsequent response to methoxamine, while nicorandil (10 μ m ), forskolin (1 μ m ), sodium nitroprusside (10 μ m ) and cromakalim (1 μ m ) totally abolished it. 6 The phorbol ester, given cumulatively, caused increasing contraction in the concentration range 30 nM‐10 μ m . Pretreatment with forskolin (1 μ m ), sodium nitroprusside (10 μ m ), isoprenaline (1 μ m ), enprofylline (10 μ m ), nicorandil (1 μ m or 10 μ m ), or cromakalim (1 μ m or 10 μ m ), resulted in partial decrease of the subsequent response to 4β‐phorbol dibutyrate. 7 These results are discussed in the light of the suggestion that protein kinase C may have a role in the ‘latch‐bridge’ phase of smooth muscle contraction, and that inappropriate activation of protein kinase C may contribute to the pathogenesis of hypertension and other conditions involving vasospasm.