RT Journal Article SR Electronic T1 Insights Into the Unusual Alpha Adrenoceptor Subtype in Dog Saphenous Vein Using Phenoxybenzamine JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 148 OP 156 VO 288 IS 1 A1 A. M. Low A1 H. Lu-Chao A1 J. C. P. Loke A1 C. Y. Kwan A1 E. E. Daniel YR 1999 UL http://jpet.aspetjournals.org/content/288/1/148.abstract AB In the dog saphenous vein (DSV), phenylephrine (PE) responses throughalpha-1 adrenoceptors receptors are antagonized by bothalpha-1 and alpha-2 receptor antagonists. Furthermore, pretreatment with chloroethylclonidine (CEC) eliminates prazosin binding but reduces rauwolscine binding by half (Daniel et al.,1996). In new functional experiments, the effects of preincubation with phenoxybenzamine (PBZ), an irreversible alphaadrenoceptor antagonist, on responses to PE and two selectivealpha-2 adrenoceptor agonists were evaluated. Also, the ability of prazosin or rauwolscine to prevent irreversible losses of responses to these agonists when coincubated with PBZ was determined. Preincubation in PBZ (10–300 nM) concentration dependently reduced PEEmax and the calculated fraction of residual receptors (q). Preincubation in PBZ (10–300 nM) increasedKB values for prazosin (30 and 100 nM) but did not alter the KB value for rauwolscine (50 nM) acting at the residual receptors from control values. Coincubation of PBZ with prazosin partially prevented these PBZ actions (Emax partly restored) on responses to PE, but coincubation of rauwolscine (≤1 μM) with PBZ, did not. Rauwolscine competitively inhibited responses to twoalpha-2 adrenoceptor agonists (Schild plot pA2 values near 9). Preincubation with PBZ concentrations of ≥300 nM caused >50% reduction in Emaxvalues of responses but did not alter the EC50 values for either agonist. Coincubation of rauwolscine with PBZ protected responses to alpha-2 agonists against PBZ (1 μM) effects. This study shows that PE initiates contractions at atypicalalpha-1 adrenoceptors represented by all sites of PE action. Rauwolscine antagonizes PE actions but does not protect against PBZ inactivation. Typical alpha-2 adrenoceptors are distinguished from the unusual alpha-1 adrenoceptors by their lesser sensitivity to PBZ and their protection by rauwolscine from PBZ. The American Society for Pharmacology and Experimental Therapeutics