Alpha-2-adrenoceptor-mediated effects of pergolide.
The alpha-adrenoceptor-mediated effects of pergolide were investigated in a number of biochemical and pharmacological test systems. In radioligand binding studies, pergolide more effectively competed for alpha 2-adrenoceptors than for alpha 1-adrenoceptors in membranes prepared from rat cerebral cortex. Consistent with this finding was the observation that pergolide was several orders of magnitude more effective in activating presynaptic alpha 2-adrenoceptors in rat vas deferens to inhibit stimulation-evoked [3H]-norepinephrine release than in activating postsynaptic alpha 1-adrenoceptors in the same tissue to produce a contractile response. Pergolide elicited a potent vasopressor response in pithed rats that was highly sensitive to antagonism by the selective alpha 2-adrenoceptor antagonist, yohimbine, and resistant to blockade by the selective alpha 1-adrenoceptor antagonist, prazosin, suggesting that pergolide selectively activates postsynaptic vascular alpha 2-adrenoceptors. The results of the present study indicate that the alpha-adrenoceptor-mediated effects commonly associated with pergolide result from selective stimulation of alpha 2-adrenoceptors.
Ruffolo
R R
RR
Department of Pharmacology, Smith Kline & French Laboratories, Swedeland, Pa.
Cohen
M L
ML
Messick
K
K
Horng
J S
JS
D000818:Animals; D003655:Decerebrate State; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010479:Pergolide / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D010479:Pergolide; D009638:Norepinephrine