CHARACTERIZATION OF ALPHA-ADRENOCEPTORS IN CANINE MESENTERIC VEIN

The alpha-adrenergic receptors (alpha-ARs) in canine mesenteric vein ( DMV) were studied by using nonselective agonists and selective antagon ists in functional studies and in ligand binding to classify the subty pes present. Based on functional studies of phenylephrine (PE)-induced contractions and ligand-binding interactions of [H-3]-prazosin with p razosin (PR), WB 4101 (WB), 5-methylurapidil (5-MU), BMY 7378, and SK& F 105854, and pretreatment with chloroethylclonidine (CEC), DMV alpha( 1)-ARs resembled the alpha(1D) subtype. However, the affinity of PR as sessed in functional and ligand-binding studies was less (PKB,D,i less than or equal to 9) than expected from previous characterization of c loned rat or human alpha(1-)AR (pK(i) greater than or equal to 10). In teractions with 5-MU, BMY 7378, or SK&F 105854 suggested the presence of some alpha(1)-ARs that were not typical of alpha(1D)-AR and that bi nding and functional interactions did not yield corresponding results. PR binding was abolished by treatment with CEC, contractile responses to PE were reduced in E-max, and the concentration-effect curve shift ed to the left, as previously reported. DMVs contracted in response to alpha(2)-AR agonists and were studied when contractions were potentia ted by increasing extracellular KCl to 20 mM. Rauwolscine (RAU) had K- B values at these sites consistent with K-D values in binding studies. CEC had no effect on RAU binding in DMV. Ligand-binding studies to [H -3]-RAU sites did not reveal a clear identification of subtype, but th ese alpha(2)-ARs were clearly not alpha(2B)-ARs. We conclude that cani ne mesenteric vein contains alpha(1D)-like ARs, but with significant d ifferences, and an unclassifiable alpha(2)-AR. There may also be a sma ller population of other, not alpha(1D)-like ARs, receptors, mediating responses to PE and binding of prazosin.