lithium-chloride and chlorethylclonidine

The relative contributions of the alpha 1A- and alpha 1B-adrenoceptor subtypes to the stimulation of phosphoinositide (PI) hydrolysis in rat and rabbit ventricular myocardium were defined pharmacologically using WB-4101 and chloroethylclonidine (CEC). Radioligand binding experiments with [3H]prazosin showed that the maximum number of alpha 1A-adrenoceptors in rat myocardium was about ten times higher than in rabbit myocardium. The proportion of the two [3H]prazosin binding sites with high and low affinity for WB-4101 was similar in the two species: approximately 30% of the alpha 1-adrenoceptor population was pharmacologically alpha 1A and approximately 70% was alpha 1B. Phenylephrine produced concentration-dependent stimulation of PI hydrolysis in rat ventricular strips as measured by [3H]inositol monophosphate accumulation, but this stimulation was much less in rabbit. In both of the two species, WB-4101 was very effective in inhibiting phenylephrine-stimulated PI hydrolysis, whereas CEC had a minimal effect. Altogether, the degree of PI hydrolysis appears to be determined by the density of myocardial alpha 1-adrenoceptors. However, despite the greater density of the alpha 1B-subtype, it is the alpha 1A-subtype that is mainly coupled to PI hydrolysis in mammalian myocardium.

Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Clonidine; Dioxanes; Female; Heart Ventricles; Hydrolysis; Kinetics; Lithium Chloride; Male; Myocardium; Phosphatidylinositols; Prazosin; Rabbits; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-1; Tritium

Administration to rats of dietary lithium for 30 days was followed by evaluation of alpha-1 adrenergic receptor binding and of adrenergic-stimulated cyclic AMP (cAMP) accumulation in rat cerebral cortex. Chronic lithium treatment did not alter the binding characteristics of [3H]prazosin or the proportion of alpha-1 adrenergic receptor subtypes distinguished by chlorethyl-clonidine (CEC) pretreatment in rat cerebral cortical membranes. Accumulation of cAMP in cortical slices incubated with adrenergic agonists was unaffected in lithium-treated rats. These results demonstrate that chronic lithium treatment-induced reduction of norepinephrine (NE)-stimulated phosphoinositide (PI) hydrolysis (Casebolt and Jope, 1987) is not due to changes in the alpha-1 adrenergic receptor and is more sensitive to in vivo lithium treatment than is adrenergic-stimulated cAMP accumulation.

Topics: Administration, Oral; Adrenergic alpha-Agonists; Animals; Cerebral Cortex; Chlorides; Clonidine; Cyclic AMP; Lithium; Lithium Chloride; Male; Norepinephrine; Phosphatidylinositols; Prazosin; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha; Second Messenger Systems