Identification of alpha 1-adrenoceptor subtypes present in the human prostate

α 1 -Adrenoceptors (ARs) play an important role in mediating human prostatic smooth muscle contraction. In the present study cDNA fragments covering different domains of 3 α 1 -AR subtypes ( α 1b , α 1c and α 1d ) were generated from human prostate by reverse transcription coupled to the polymerase chain reaction (RT-PCR). The reconstituted partial sequence (349 amino acids) of the human prostatic α 1c-AR PCR products showed 94% identity at the amino acid level with that of the corresponding region of the cloned bovine brain α 1c -AR. Using human α 1 -AR subtype selective cDNA probes in Northern blot analysis, the co-expression of mRNA transcripts corresponding to α 1b -, α 1c - and α 1d -AR subtypes was detected in 4 different regions (apex, base, periurethra and lateral lobe) of the human prostate. Competitive inhibition experiments of [ 3 H]-prazosin binding to membrane preparations of human prostate revealed that the non-selective α 1 -subtype antagonist, alfuzosin, produced a monophasic inhibition curve, whereas oxymetazoline produced a 2-component inhibition curve with pK i values of 8.54 and 5.46. The high-affinity α 1 -AR component of the oxymetazoline inhibition curve was predominant (57%–66%) and showed an affinity for oxymetazoline comparable to that of the α 1 c -AR subtype. As such our results illustrate the expression of different α 1 -AR subtypes in human prostate and importantly that α 1c represents the predominant α 1 -AR subtype present in this tissue.