Premium
Phorbol esters inhibit smooth muscle contractions through activation of Na + ‐K + ‐ATPase
Author(s) -
Sasaguri Toshiyuki,
Watson Stephen P.
Publication year - 1990
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.1476-5381.1990.tb14687.x
Subject(s) - carbachol , ouabain , phorbol , chemistry , histamine , protein kinase c , medicine , endocrinology , agonist , tonic (physiology) , stimulation , receptor , biochemistry , sodium , biology , phosphorylation , organic chemistry
1 The role of protein kinase C (PKC) in agonist‐induced contractions of guinea‐pig ileum longitudinal smooth muscle has been investigated. 2 The phorbol esters, phorbol 12,13‐dibutyrate (PDBu), phorbol 12,13‐diacetate (PDA) and phorbol 12‐myristate 13‐acetate (PMA), relaxed tissues precontracted by submaximal concentrations of carbachol, histamine or substance P. 3 This inhibitory action of the phorbol esters was reversed following the application of ouabain, a specific inhibitor of Na + ‐K + ‐ATPase. Similarly, pretreatment with ouabain inhibited the ability of phorbol esters to relax tissues precontracted by the above agonists. 4 The slow relaxation of the tonic component of contraction induced by submaximal concentrations of carbachol and histamine, and all concentrations of substance P, was abolished in the presence of ouabain. 5 In Na + ‐loaded tissues, PDBu and carbachol caused a concentration‐dependent increase of Na + ‐K + ‐ATPase activity, assessed by ouabain‐sensitive 86 Rb + ‐uptake. Extrusion of Na + , assessed by the cellular content of the ion, was also stimulated by PDBu (the effect of carbachol was not investigated). 6 We conclude that phorbol esters inhibit the tonic component of contractions induced by submaximal concentrations of these agonists through activation of Na + ‐K + ‐ATPase. We suggest that PKC may exert feedback control over the tonic component of agonist contractions through stimulation of the pump.