Displacement by alpha-adrenergic agonists and antagonists of 3H-prazosin bound to the alpha-adrenoceptors of the dog aorta and the rat brain.

To characterize the alpha 1-adrenoceptors in the dog aorta and the rat brain and to assess the antagonistic potencies of various chemicals inclusive of newly synthesized ones, radioligand binding assays were performed, and the potencies thus obtained were compared with those obtained from pharmacological observations. Reproducible binding to and displacement from the dog aorta of 3H-prazosin were observed. The rank orders of the inhibition of 3H-prazosin binding to the membrane preparations of the aorta expressed as IC50 (the concentration of drugs inhibiting 50% of maximal specific binding of 3H-prazosin) were: prazosin greater than YM09538 greater than phentolamine greater than yohimbine greater than phenoxybenzamine greater than labetalol greater than S-596 greater than dibenamine greater than K-351 greater than propranolol greater than hydralazine greater than N-696 for alpha-blockers and I-epinephrine greater than clonidine greater than I-norepinephrine greater than phenylephrine greater than I-isoproterenol for agonists. IC50 values of phenoxybenzamine, labetalol, dibenamine and K-351 obtained in the brain preparations were higher than those obtained in the preparation of the aorta. There was a good correlation (r = 0.90) between the IC50 values obtained in the dog aorta and in the rat brain, suggesting that the alpha 1-adrenergic receptors in the dog aorta and the rat brain resemble each other. Good correlations (aorta, r=0.97 and brain, r=0.94) were also observed between IC50 values derived from the binding assay in the aorta or the brain and the pA2 values obtained as regards to the contractile response of the rat aorta to phenylephrine. Thus, this method could be useful for the assessment of newly synthesized chemicals as alpha-adrenergic antagonists.