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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Anisuzzaman, A. S. M. Muramatsu, I. Yoshiki, H. Uwada, J. Umada, H. Nishimune, A. |
| Description | Author Affiliation: Nishimune A ( Division of Pharmacology, Department of Biochemistry and Bioinformative Sciences, Organization for Life Science Advancement Programs, and Child Development Research Center, School of Medicine, University of Fukui, Eiheiji, Fukui, Japan.) |
| Abstract | (1)-Adrenoceptors are involved in numerous physiological functions, including micturition. However, the pharmacological profile of the (1)-adrenoceptor subtypes remains controversial. Here, we review the literature regarding (1)-adrenoceptors in the lower urinary tract from the standpoint of (1L) phenotype pharmacology. Among three (1)-adrenoceptor subtypes ( (1A), (1B) and (1D)), (1a)-adrenoceptor mRNA is the most abundantly transcribed in the prostate, urethra and bladder neck of many species, including humans. In prostate homogenates or membrane preparations, (1A)-adrenoceptors with high affinity for prazosin have been detected as radioligand binding sites. Functional (1)-adrenoceptors in the prostate, urethra and bladder neck have low affinity for prazosin, suggesting the presence of an atypical (1)-adrenoceptor phenotype (designated as (1L)). The (1L)-adrenoceptor occurs as a distinct binding entity from the (1A)-adrenoceptor in intact segments of variety of tissues including prostate. Both the (1L)- and (1A)-adrenoceptors are specifically absent from Adra1A ( (1a)) gene-knockout mice. Transfection of (1a)-adrenoceptor cDNA predominantly expresses (1A)-phenotype in several cultured cell lines. However, in CHO cells, such transfection expresses (1L)- and (1A)-phenotypes. Under intact cell conditions, the (1L)-phenotype is predominant when co-expressed with the receptor interacting protein, CRELD1 . In summary, recent pharmacological studies reveal that two distinct (1)-adrenoceptor phenotypes ( (1A) and (1L)) originate from a single Adra1A ( (1a)-adrenoceptor) gene, but adrenergic contractions in the lower urinary tract are predominantly mediated via the (1L)-adrenoceptor. From the standpoint of phenotype pharmacology, it is likely that phenotype-based subtypes such as the (1L)-adrenoceptor will become new targets for drug development and pharmacotherapy. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 165 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2012-03-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Adrenergic Alpha-1 Receptor Antagonists Pharmacology Prazosin Receptors, Adrenergic, Alpha-1 Metabolism Urinary Tract Drug Effects Therapeutic Use Animals Phenotype Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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