Detection of α1-adrenoceptor subtypes in human hypertrophied prostate byin situ hybridizationsubtypes in human hypertrophied prostate byin situ hybridization

Abstract

Adrenergic stimulation induces contraction of hypertrophied prostatic tissue via the alpha 1 adrenoceptor, and the results of pharmacological studies suggested the existence of adrenoceptor subtypes. Recently three subtypes (alpha 1a, alpha 1b, and alpha 1d) were cloned. Using probes for these subtypes, we demonstrated their expression in the tissues of ten cases of benign prostatic hypertrophy, using in situ hybridization. To determine the ratio between these subtypes, an RNase protection assay was also performed in three cases. Expression of the alpha 1a and alpha 1d adrenoceptors was diffuse in the smooth muscles of the interstitium, but was absent in glandular epithelial cells. On the contrary, the alpha 1b adrenoceptor was hardly detectable. The RNase protection assay confirmed the absence of the alpha 1b adrenoceptor, the ratio of alpha 1a and alpha 1d being 4:1. These results supported the idea that the differences in prostatic contractile response to several adrenergic drugs are based on the affinities of these drugs for the different subtypes.

Mechanistic insights into the role of α1-adrenergic receptors in lower urinary tract symptoms

“…A recent study by Nasu et al [32] showed that 69.3%, 3.3%, and 27.3% of the α 1 ARs in the prostate are subtypes α 1a , α 1b , and α 1d , respectively. When only patients with BPH are observed, a different pattern is observed, with the α 1a AR subtype increasing to 85%, α 1d AR decreasing to 14%, and negligible amounts of subtype α 1b AR detected [32,33]. This has been confirmed at a protein level through contraction assays of human prostate smooth muscle [26,27,32,34].…”

Quantification and distribution of α1‐adrenoceptor subtype mRNAs in human prostate: comparison of benign hypertrophied tissue and non‐hypertrophied tissue

“…The al-adrenoceptor subtypes expressed in human prostate have been pharmacologically characterized by radioligand binding assay (Muramatsu et al, 1994;Chapple et al, 1994) and the'expression of the three subtype mRNAs has been examined by an RNase protection assay and in situ hybridization (Price et al, 1993b;Moriyama et al, 1996 (Price et al, 1993b;Moriyama et al, 1996). However, we found a major difference between BPH and non-BPH samples: the total abundance of xl-adrenoceptor mRNA in BPH samples was over six times that in non-BPH samples, and the abundance of axl a mRNA in BPH samples was almost nine times that in non-BPH samples.…”

“…In addition, some of these antagonists also have side effects, such as a lowering of blood pressure. Several groups have used both functional and radioligand binding assays (Michel et al, 1994;Foglar et al, 1995) and in situ hybridization (Price et al, 1993b;Moriyama et al, 1996) to investigate al-adrenoceptor subtypes in the human prostate, and the results indicate that ala is the major subtype. These findings led to the development of prostateselective drugs that cause few side effects (Kawabe et al, 1994 Chomczymski & Sacchi (1987).…”

Effect of KMD‐3213, an α1A‐adrenoceptor antagonist, on the prostatic urethral pressure and blood pressure in male decerebrate dogs

“…In particular, the a 1A -adrenoceptor is preferentially expressed in human prostate, 4 especially in the hypertrophied prostate. 5,6 Moreover, the contractile response to norepinephrine is mediated by the a 1A -adrenoceptor. 7 These findings suggest an a 1A -adrenoceptor antagonist specific for the prostate may be achievable.…”