Indirect evidence for a role of phosphatidylinositol turnover in the cardiac response to H1-receptor stimulation.
The influence of lithium on the positive inotropic effect of the H1-agonist 2-pyridyl-ethylamine (PEA) and of the H2-receptor agonist 4-methylhistamine was studied in isolated guinea-pig ventricular strips electrically stimulated at 1 Hz. Lithium (1-10 mM) was devoid of any effect on cardiac contraction; the positive inotropic effect of 4-methylhistamine was unaffected in the presence of 10 mM lithium. On the other hand, lithium (1-10 mM) dose-dependently shifted the dose-inotropic effect curve for PEA to the right; an antagonistic effect, qualitatively similar to that of lithium, was induced by the myoinositol antagonist 2-2'-anhydro-2-C-hydroxymethyl-myoinositol, at a concentration of 100 microM. Moreover the antagonistic effect of the higher lithium concentration (10 mM) was almost completely prevented in preparations superfused with 10 mM myoinositol. Since it is known that lithium is able to reduce the cellular availability of myoinositol by an interference with the phosphatidylinositol (PI) cycle, these results suggest that the H1-receptor-mediated increase in contractility may be linked to an increased turnover of PI, while the H2-receptor-mediated one is not.
Mantelli
L
L
Department of Pharmacology, University of Florence, Italy.
Ledda
F
F
Capanni
L
L
Corti
V
V
D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000187:drug effects*
D010716:Phosphatidylinositols; D011725:Pyridines; D011969:Receptors, Histamine H1; D008094:Lithium; C006183:2-(2-aminoethyl)pyridine