{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T12:23:47Z","timestamp":1743596627419,"version":"3.38.0"},"reference-count":98,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,2,10]],"date-time":"2012-02-10T00:00:00Z","timestamp":1328832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p>\u03b1<jats:sub>1<\/jats:sub>\u2010Adrenoceptors are involved in numerous physiological functions, including micturition. However, the pharmacological profile of the \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptor subtypes remains controversial. Here, we review the literature regarding \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptors in the lower urinary tract from the standpoint of \u03b1<jats:sub>1L<\/jats:sub>phenotype pharmacology. Among three \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptor subtypes (\u03b1<jats:sub>1A<\/jats:sub>, \u03b1<jats:sub>1B<\/jats:sub>and \u03b1<jats:sub>1D<\/jats:sub>), \u03b1<jats:sub>1a<\/jats:sub>\u2010adrenoceptor mRNA is the most abundantly transcribed in the prostate, urethra and bladder neck of many species, including humans. In prostate homogenates or membrane preparations, \u03b1<jats:sub>1A<\/jats:sub>\u2010adrenoceptors with high affinity for prazosin have been detected as radioligand binding sites. Functional \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptors in the prostate, urethra and bladder neck have low affinity for prazosin, suggesting the presence of an atypical \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptor phenotype (designated as \u03b1<jats:sub>1L<\/jats:sub>). The \u03b1<jats:sub>1L<\/jats:sub>\u2010adrenoceptor occurs as a distinct binding entity from the \u03b1<jats:sub>1A<\/jats:sub>\u2010adrenoceptor in intact segments of variety of tissues including prostate. Both the \u03b1<jats:sub>1L<\/jats:sub>\u2010 and \u03b1<jats:sub>1A<\/jats:sub>\u2010adrenoceptors are specifically absent from<jats:italic>Adra1A<\/jats:italic>(\u03b1<jats:sub>1a<\/jats:sub>) gene\u2010knockout mice. Transfection of \u03b1<jats:sub>1a<\/jats:sub>\u2010adrenoceptor cDNA predominantly expresses \u03b1<jats:sub>1A<\/jats:sub>\u2010phenotype in several cultured cell lines. However, in CHO cells, such transfection expresses \u03b1<jats:sub>1L<\/jats:sub>\u2010 and \u03b1<jats:sub>1A<\/jats:sub>\u2010phenotypes. Under intact cell conditions, the \u03b1<jats:sub>1L<\/jats:sub>\u2010phenotype is predominant when co\u2010expressed with the receptor interacting protein, CRELD1\u03b1. In summary, recent pharmacological studies reveal that two distinct \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptor phenotypes (\u03b1<jats:sub>1A<\/jats:sub>and \u03b1<jats:sub>1L<\/jats:sub>) originate from a single<jats:italic>Adra1A<\/jats:italic>(\u03b1<jats:sub>1a<\/jats:sub>\u2010adrenoceptor) gene, but adrenergic contractions in the lower urinary tract are predominantly mediated via the \u03b1<jats:sub>1L<\/jats:sub>\u2010adrenoceptor. From the standpoint of phenotype pharmacology, it is likely that phenotype\u2010based subtypes such as the \u03b1<jats:sub>1L<\/jats:sub>\u2010adrenoceptor will become new targets for drug development and pharmacotherapy.<\/jats:p><jats:p><jats:bold>LINKED ARTICLE<\/jats:bold>This article is commented on by Ventura, pp. 1223\u20131225 of this issue. To view this commentary visit<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/j.1476-5381.2011.01663.x\">http:\/\/dx.doi.org\/10.1111\/j.1476\u20105381.2011.01663.x<\/jats:ext-link><\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01591.x","type":"journal-article","created":{"date-parts":[[2011,7,11]],"date-time":"2011-07-11T12:07:25Z","timestamp":1310386045000},"page":"1226-1234","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Phenotype pharmacology of lower urinary tract 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