Identification of α1-adrenoceptor subtypes present in the human prostate
1994; Elsevier BV; Volume: 54; Issue: 21 Linguagem: Inglês
10.1016/0024-3205(94)90031-0
ISSN1879-0631
AutoresCécile Faure, C. Pimoule, G Vallancien, Salomón Z. Langer, David Y. Graham,
Tópico(s)Hormonal and reproductive studies
Resumoα1-Adrenoceptors (ARs) play an important role in mediating human prostatic smooth muscle contraction. In the present study cDNA fragments covering different domains of 3 α1-AR subtypes (α1b, α1c and α1d) 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 α1c-AR PCR products showed 94% identity at the amino acid level with that of the corresponding region of the cloned bovine brain α1c-AR. Using human α1-AR subtype selective cDNA probes in Northern blot analysis, the co-expression of mRNA transcripts corresponding to α1b-, α1c- and α1d-AR subtypes was detected in 4 different regions (apex, base, periurethra and lateral lobe) of the human prostate. Competitive inhibition experiments of [3H]-prazosin binding to membrane preparations of human prostate revealed that the non-selective α1-subtype antagonist, alfuzosin, produced a monophasic inhibition curve, whereas oxymetazoline produced a 2-component inhibition curve with pKi values of 8.54 and 5.46. The high-affinity α1-AR component of the oxymetazoline inhibition curve was predominant (57%–66%) and showed an affinity for oxymetazoline comparable to that of the α1c-AR subtype. As such our results illustrate the expression of different α1-AR subtypes in human prostate and importantly that α1c represents the predominant α1-AR subtype present in this tissue.
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