Regulation of angiotensin II receptors in the prostate of the transgenic (mRen-2)27 rat: effect of angiotensin-converting enzyme inhibition.
We examined the regulation/expression of angiotensin II (Ang II) receptors in the transgenic (TG) (mRen-2)27 rat compared to the normal Sprague-Dawley (SD) rat. Ang II receptor binding and mRNA expression were determined by quantitative autoradiography and real-time PCR, respectively. Ang II receptors in the rat prostate rat were of the AT(1) receptor subtype and were significantly reduced in the prostate of the TG rat compared to the normal SD rat. However, AT(1) receptor binding was significantly higher in the prostate of the TG rat treated with the ACE inhibitor lisinopril compared to the untreated TG rat and comparable to the control SD rat. In contrast to the protein, AT(1) receptor mRNA expression was not reduced in the prostate of the TG rat compared to the SD rat. However, AT(1) receptor mRNA was markedly reduced in the prostate of the lisinopril-treated TG rat compared to the untreated TG rat or control SD rat. In conclusion, the findings suggest that AT(1) receptors are present in the rat prostate at a protein level and are subject to down-regulation in the TG rat which may be due to receptor internalisation as a consequence of receptor hyper-stimulation by increased local tissue levels of Ang II. Moreover, AT(1) receptor protein and mRNA expression in the prostate may be inversely modulated.
Fabiani
Maurice E
ME
Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, VIC 3084, Australia. m.fabiani@austin.unimelb.edu.au
Hawkes
David J
DJ
Frauman
Albert G
AG
Tikellis
Chris
C
Johnston
Colin I
CI
Wilkinson-Berka
Jennifer L
JL
D048868:Adaptor Proteins, Signal Transducing; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D001345:Autoradiography; D002352:Carrier Proteins / Q000096:biosynthesis*; D015536:Down-Regulation; D017706:Lisinopril / Q000494:pharmacology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000096:biosynthesis* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; C119712:Agtrap protein, mouse; D000806:Angiotensin-Converting Enzyme Inhibitors; D002352:Carrier Proteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A