Effect of angiotensins on electrogenic anion transport in monolayer cultures of rat epididymis.
Confluent monolayers cultured from the rat cauda epididymidis have been shown to respond to angiotensin I (AI) and angiotensin II (AII) when studied under short-circuit conditions and bathed on both sides with Krebs-Henseleit solution. Both the decapeptide AI and the octapeptide AII elicited transient increases in short-circuit current (SCC) when added to the basolateral as well as to the apical surfaces, with the effect of basolateral application greater than that of apical application. The maximal responses produced by AI and AII were similar with median effective concentrations of 20 to 80 nmol/l. The increase in SCC by AII was dependent upon extracellular Cl- and was inhibited by addition of a Cl- channel blocker, diphenylamine 2-carboxylate, to the apical surface. These patterns of activity suggest that the SCC responses to angiotensins result from electrogenic chloride secretion. Pretreating the monolayers with captopril (100 nmol/l), an angiotensin-converting enzyme (ACE) inhibitor, reduced the response to basolateral application of AI, but completely abolished the response to AI added apically. These results suggest that the response to apical addition of AI was due to conversion of AI to AII which interacts with apical angiotensin receptors. This conversion was mediated by ACE which has been detected in epididymal monolayers. Of the endogenous ACE activity, 86% was found to be inhibited by captopril (100 nmol/l). Responses of the epididymal monolayers to angiotensins were mediated by specific angiotensin receptors. [Sar1,Ile8]-AII, a specific antagonist of the AII receptor, completely inhibited the responses to AI and AII but had no effect on the responses to bradykinin and endothelin.(ABSTRACT TRUNCATED AT 250 WORDS)
Wong
P Y
PY
Department of Physiology, University of Hong Kong.
Fu
W O
WO
Huang
S J
SJ
Law
W K
WK
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D000838:Anions / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D004822:Epididymis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats
D000809:Angiotensins; D000838:Anions; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D000242:Cyclic AMP; D007703:Peptidyl-Dipeptidase A