Lithium increases the alpha 1-adrenoceptor mediated inotropic effect in rat heart.
The intracellular mechanisms activated by stimulation of myocardial alpha 1-adrenoceptors are not known. As in several other tissues, however, activation of alpha 1-adrenoceptors in heart has been related to breakdown of phosphoinositides resulting in production of putative intracellular messengers: different inositol phosphates and diacylglycerol. Lithium has been shown to inhibit enzymes hydrolyzing inositol phosphates. In the present paper we report studies on the effect of lithium upon the alpha 1-adrenoceptor mediated inotropic response elicited in electrically driven rat papillary muscles. While there was no shift of the horizontal positioning of the dose-response curve to alpha 1-adrenergic stimulation in the presence of lithium, the alpha 1-adrenoceptor mediated inotropic effect was increased in a concentration dependent manner (0.25 to 3.0 mmol/l lithium). For comparison, the effect of lithium upon the beta-adrenoceptor mediated inotropic response was also studied. At 3.0 mmol/l lithium, the horizontal position of the dose-response curve to beta-adrenoceptor stimulation was shifted significantly to the right (to higher agonist concentrations) and the maximal beta-adrenoceptor mediated inotropic response was slightly although not significantly reduced. Thus the augmenting effect of lithium upon the alpha 1-adrenoceptor mediated response was specific for this receptor type. Although the effect of lithium may be complex, the data are compatible with the hypothesis that the inositol phosphates may be of functional importance during stimulation of myocardial alpha 1-adrenoceptors.
Skomedal
T
T
Department of Pharmacology, University of Oslo, Norway.
Schiander
I G
IG
Husøy
E A
EA
Tveiten
A
A
Osnes
J B
JB
D000818:Animals; D066298:In Vitro Techniques; D008094:Lithium / Q000502:physiology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D008094:Lithium