Demonstration of alpha 1-adrenoceptors in guinea pig lung using 3H-prazosin.

³H-prazosin, a new radioligand of high specific radioactivity (33 Ci/mmol) was used to characterise postsynaptic (α₁) adrenoceptors in guinea pig lung membranes. Binding was saturable and of high affinity (K_D 0.24 nM) with a Bmax of 54 fmol/mg protein. Adrenergic agonists competed for binding in the order (?)-epinephrine > (?)-norepinephrine ? (?)-phenyl-ephrine > (?)-isoproterenol. (+)-norepinephrine was 100x less potent than (?)-norepinephrine. α-Adrenergic antagonists competed in the order prazosin > WB 4101 > indoramin > phentolamine > haloperidol > chlorpromazine ? piperoxan > yohimbine, indicating that ³H-prazosin binding is probably to α₁-adrenoceptors. Propranolol, methysergide and sulpiride inhibited binding only at high concentrations. Binding of (?)-³H-dihydroalprenolol under identical experimental conditions gave a K_D of 0.93 nM and a Bmax of 870 fmol/mg protein, giving a ratio of beta : α-adrenoceptor binding sites of 16 : 1 in this lung membrane preparation. ³H-prazosin appears to be a useful ligand in studying α₁-adrenoceptors.