Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9341
Title: Angiotensin II enhances noradrenaline release from sympathetic nerves of the rat prostate via a novel angiotensin receptor: implications for the pathophysiology of benign prostatic hyperplasia.
Authors: Fabiani, Mark E;Sourial, M;Thomas, W G;Johnston, Colin I;Frauman, Albert G
Affiliation: Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg VIC 3084, Australia. m.fabiani@austin.unimelb.edu.au
Issue Date: 1-Oct-2001
Citation: The Journal of Endocrinology; 171(1): 97-108
Abstract: The renin-angiotensin system (RAS) is present in the human prostate and may be activated in benign prostatic hyperplasia (BPH), possibly contributing to the pathophysiology of this disorder by enhancing local sympathetic tone and cell growth. The functional role of the RAS in the prostate, however, is unknown. The present study was undertaken to determine whether angiotensin (Ang) II enhances sympathetic transmission in the prostate. The neuronal stores of the rat prostate were labelled with [(3)H]noradrenaline (NA). Ang II and Ang I enhanced [(3)H]NA release in a concentration-dependent manner. The Ang II receptor subtype 1 (AT(1) receptor) antagonist losartan and the AT(2) receptor antagonist PD123319 inhibited this facilitatory effect of Ang II and Ang I, whereas the other AT(2) receptor antagonist, CGP42112, was without effect. Bradykinin also increased [(3)H]NA release, which was inhibited by the B(2) receptor antagonist Hoe140. The angiotensin-converting enzyme inhibitor captopril inhibited the effect of Ang I, but potentiated that of bradykinin. Interestingly, captopril alone produced an increase in [(3)H]NA release which was inhibited by Hoe140. Losartan, but not PD123319 or CGP42112, inhibited [(125)I]-Ang II binding in Chinese hamster ovary cells transfected with the AT(1a) or AT(1b) receptor. In contrast, in cells expressing the AT(2) receptor, PD123319 and CGP42112, but not losartan, inhibited [(125)I]-Ang II binding. In conclusion, Ang II enhances the release of NA from sympathetic nerves of the rat prostate via a novel functional receptor distinct from the cloned AT(1a), AT(1b) or AT(2). These data provide direct evidence in support of a functional role for the local RAS in modulating sympathetic transmission in the prostate, which may have important implications for the pathophysiology of BPH.
Internal ID Number: 11572794
URI: http://ahro.austin.org.au/austinjspui/handle/1/9341
URL: http://www.ncbi.nlm.nih.gov/pubmed/11572794
Type: Journal Article
Subjects: Analysis of Variance
Angiotensin I.pharmacology
Angiotensin II.pharmacology
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors.pharmacology
Animals
Bradykinin.analogs & derivatives.pharmacology
CHO Cells.drug effects
Captopril.pharmacology
Cricetinae
Dose-Response Relationship, Drug
Imidazoles.pharmacology
Losartan.pharmacology
Male
Norepinephrine.secretion
Oligopeptides.pharmacology
Prostate.innervation
Prostatic Hyperplasia.physiopathology
Pyridines.pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Angiotensin.metabolism
Sympathetic Nervous System.drug effects.secretion
Synaptic Transmission.drug effects
Appears in Collections:Journal articles

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