Quantification and distribution of α₁-adrenoceptor subtype mRNAs in human vas deferens: comparison with those of epididymal and pelvic portions

Abstract

1. This study was intended to quantify the amounts of the α₁-adrenoceptor subtype mRNAs in human vas deferens, and demonstrate the receptor subtype responsible for the vas contraction.

2. The RNase protection assay showed that the mean total amount of α_1a mRNA was 7.4±2.2 pg/5 μg of poly (A)⁺ RNA (97.0% of the total α₁ mRNA) in the epididymal portion (E-vas) and 4.9±0.8 pg/5 μg of poly (A)⁺ RNA (96.3% of the total) in the pelvic portion (P-vas). The E-vas showed a tendency to have a greater α_1a mRNA abundance than the P-vas (P=0.11). The α_1b and α_1d mRNAs were absent or of extremely low abundance.

3. By an in situ hybridization, the α_1a and α_1d mRNAs were recognized in the smooth muscle cells of the E-vas and the P-vas, and the distribution pattern the same in both tissues. The α_1b mRNA positive site was scarcely detectable in both vas portions.

4. In a functional study, l-phenylephrine produced concentration-dependent contraction in the E-vas (E_max=2.24±0.70 g; pD₂=5.32±0.09) and the P-vas (E_max=2.46±0.46 g; pD₂=5.07±0.12). KMD-3213, a novel α_1A-adrenoceptor-selective antagonist, caused parallel rightward shifts of the concentration–response curves for l-phenylephrine. Apparent pK_B values were 9.90±0.16 for the E-vas and 9.71±0.17 for the P-vas. There was no significant difference in E_max, pD₂ or pK_B estimates between the two portions.

5. We have found that α_1a mRNA is predominant in the human vas deferens, and confirmed that contraction of this organ is mediated by the α_1A-adrenoceptor.

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