Premium
Effects of carbachol and (−)‐N 6 ‐phenylisopropyladenosine on myocardial inositol phosphate content and force of contraction
Author(s) -
Kohl Claudia,
Linck Bettina,
Schmitz Wilhelm,
Scholz Hasso,
Scholz Jens,
Tóth Mathias
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.tb14165.x
Subject(s) - carbachol , medicine , endocrinology , chemistry , contraction (grammar) , inotrope , inositol , inositol phosphate , muscle contraction , stimulation , receptor , biology
1 The effects of carbachol and the A 1 ‐adenosine receptor agonist (−)‐N 6 ‐phenylisopropyladenosine (PIA) on force of contraction and inositol lipid metabolism were studied in electrically driven left auricles and papillary muscles isolated from guinea‐pig hearts. Both carbachol and PIA (0.01–10 μ m ) had concentration‐dependent negative inotropic effects in auricles. In papillary muscles PIA had no inotropic effect. Carbachol also had no inotropic effect at low concentrations (0.01–1 μ m ) but at 10–100 μ m it exerted a slight positive inotropic effect. 2 In auricles and papillary muscles both carbachol and PIA concentration‐dependently increased inositol trisphosphate (IP 3 ; significant at 1 μ m ). Accordingly phosphatidylinositol bisphosphate (PIP 2 ), the precursor of IP 3 , was reduced. All effects of carbachol and PIA were antagonized by atropine (10 μ m ) and 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX; 20 μ m ) respectively, indicating receptor‐mediated effects. 3 In auricles the negative inotropic effects of carbachol and PIA preceded the increase in IP 3 . 4 In papillary muscles the increase in IP 3 preceded the slight positive inotropic effect of carbachol, indicating that the M‐cholinoceptor‐mediated increase in IP 3 and force of contraction may be related. However, PIA showed a comparable increase in IP 3 but no inotropic effect, indicating a dissociation between those parameters. 5 In conclusion, in previous studies a close relation between increases in IP 3 and force of contraction has been shown after α 1 ‐adrenoceptor stimulation. The present study with carbachol supports this view. However, the present data for PIA could not show such a close relationship, questioning the role of IP 3 as an endogenous regulator of force of contraction.