PHARMACOLOGICAL CHARACTERIZATION OF ADRENERGIC-RECEPTORS OF A RABBIT CEREBRAL-ARTERY INVITRO

Abstract

In the light of controversy over the functional significance of the abundant sympathetic innervation of large cerebral blood vessels, an in vitro analysis of the adrenergic receptors mediating contractile effects in the rabbit basilar artery was undertaken. .beta.-Adrenergic stimulation had no effect, and agents that block norepinephrine (NE) uptake did not alter contractile responses to l-NE. The l-NE dose-response curve could be resolved into 2 component S-shaped curves: the 1st had an ED50 of 10-5 M and reached a plateau at 10-4 M; the 2nd component continued above 10-3 M without reaching a plateau. Phenylephrine and epinephrine dose-response curves were also biphasic; d-NE responses corresponded to the 2nd phase of the l-NE curve. Relative potencies for the 2 components were different. For the 1st component, these were 1:0.23:0.18:0.03 for l-NE, epinephrine, phenylephrine and d-NE, respectively; relative potencies for the 2nd component of the curve were 1:1:0.11:0.23. Phentolamine dissociation constants were analyzed separately for each component. The value for low l-NE concentrations was 5 .times. 10-8 M and, for higher concentrations, 3 .times. 10-6 M. The insensitivity of the .alpha.-adrenergic receptor and the poor responsiveness of the muscle to its activation with agonist concentrations below 10-4 M can probably account for the small contractile responses to nerve stimulation of large pial arteries in spite of their abundant innervation.