alpha(1A)- and alpha(1B)-adrenoceptors are the major subtypes in human saphenous vein

In this study we analyzed the different alpha (1)-adrenoceptor (AR) subtype s present in human saphenous vein (HSV) using reverse transcription polymer ase chain reaction (RT-PCR), DNA-DNA hybridization analysis and functional affinities for alpha -AR antagonists. DNA-DNA hybridization analysis of RT- PCR amplification products confirmed the presence of alpha (1A)- and alpha (1B)-ARs, and low levels of alpha (1D)-AR in HSV. The functional results sh owed: (1) prazosin, the selective alpha (1)-AR antagonist, phentolamine, th e alpha (1)- and alpha (2)-ARs antagonist, WB 4101 and 5-MU, the selective alpha (1A)-AR subtype antagonists were potent, competitive antagonists of n oradrenaline (NA)-induced contraction (pA(2) values of 1 1.03, 8.06, 9.02 a nd 8.34, respectively). (2) alpha (1)-AR-induced contraction was sensitive to the alkylating effects of CEC (the alpha (1B) and alpha (1D)-AR subtypes antagonist) and (3) The selective alpha (1D)-AR subtype antagonist BMY dis played low affinity (pA(2) values of 6.44). This indicates that the contrac tile response of the HSV to alpha (1)-AR-induced is predominantly mediated by both alpha (1A) and alpha (1B)-AR subtypes. This was also supported by t he good relationship between pA(2) values from the present study and report ed binding affinities (pK(i)) values of various alpha (2)-AR subtype antago nists with cloned human alpha (1A)- and alpha (1B)-AR subtypes (r=0.89 and r=0.98, respectively), but not the alpha (1D)-AR subtype (r=0.67). Our resu lts indicate that alpha (1A)- and alpha (1B)-ARs are the main functional an d expressed receptor subtypes in HSV. (C) 2001 Elsevier Science Inc. All ri ghts reserved.