John W. Funder

The action of corticosterone on schedule-induced wheelrunning.

Previous studies have shown that schedule-induced wheelrunning is dependent on an intact pituitary-adrenal axis, and thus the presence of circulating corticosterone. In the present study, the mechanism of action of corticosterone on schedule-induced wheelrunning was explored in two ways. In the first series of studies, the effect of different levels of corticosterone on schedule-induced wheelrunning in adrenalectomized rats was investigated; the results of this study show a dose-response relationship between levels of corticosterone and schedule-induced wheelrunning. In the second study, the glucocorticoid receptor subtype involved was determined by examining the effect of dexamethasone, a synthetic glucocorticoid, on schedule-induced wheelrunning in adrenalectomized rats. A low dose of dexamethasone effectively reversed the suppressant effect of adrenalectomy, suggesting that the behavioural action of glucocorticoids is mediated through classical (Type II) glucocorticoid receptors, and not through Type I, corticosterone-preferring receptors.

Investigation of cardiac β-adrenoceptors using 125I-labelled 1-(4-iodophenoxy)-3-isopropylaminopropan-2-ol☆

1-(4-iodophenoxy)-3-isopropylaminopropan-2-ol (IIP) is a potent beta-adrenergic antagonist which has been labelled to high specific activity with 125I and used to bind to rat myocardial membranes. The characteristics of binding were consistent with the known properties of beta-receptors. Thus, binding was highly stereospecific for the L-stereoisomer since L-propranolol was two orders of magnitude more potent than the D-isomer in competing for these sites. The beta-adrenergic agonists isoproterenol, epinephrine and norepinephrine competed for binding with potencies paralleling their pharmacological potencies as beta-adrenergic effectors. The dissociation constant for binding of IIP was 4--5 nM as measured either by direct binding studies or by its inhibition of isoproterenol stimulated adenylate cyclase. Binding was saturable with 0.06 pmoles of IIP per mg of membrane protein binding at saturation. 125IIP is a high affinity, high specific activity ligand suitable for use as a selective probe for the detection and quantitation of cardiac beta-receptors. Its introduction should help solve the problems involved in the investigation of myocardial beta-adrenergic receptors.