Angiotensin II receptors are coupled to omega-conotoxin-sensitive calcium influx in bovine adrenal medullary chromaffin cells.
The contribution of an omega-conotoxin GVIA (omega Cgtx)-sensitive Ca2+ influx pathway to the effects of angiotensin II (AII) receptor activation was examined in bovine adrenal medullary (BAM) cells. Pretreatment of BAM cells with 10(-6) M omega Cgtx blocked stimulation of exocytosis by the degradation-resistant analogue, sarcosine1-angiotensin II (S1-AII). In contrast, omega Cgtx had no effect on basal secretion, nor did it inhibit [3H]norepinephrine and [32P]ATP release in response to bradykinin, another phospholipase C-linked receptor agonist. Similarly, omega Cgtx pretreatment inhibited the stimulation of 45Ca2+ uptake by S1-AII, but did not affect the response to bradykinin. This selective inhibition did not appear to be due to blockade of AII receptors by omega Cgtx, as the accumulation of 3H-labeled inositol phosphates in response to S1-AII was not inhibited. The peak S1-AII-stimulated increase in the intracellular free Ca2+ concentration (Cai) in fura 2-loaded BAM cells also was not significantly reduced by omega Cgtx (or by stimulating in nominally Ca(2+)-free buffer), indicating that this response is dependent on intracellular Ca2+ pools. However, a small omega Cgtx-sensitive Cai response was detected after depletion of intracellular Ca2+ pools with ionomycin. This study shows that AII receptors, but not bradykinin receptors, are linked to an omega Cgtx-sensitive Ca2+ influx pathway in BAM cells.
McMillian
M K
MK
Neuropharmacology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Tuominen
R K
RK
Hudson
P M
PM
Suh
H H
HH
Hong
J S
JS
D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011945:Receptors, Angiotensin / Q000378:metabolism*; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D010456:Peptides, Cyclic; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C032651:angiotensin II, Sar(1)-Ile(5)-; D015759:Ionomycin; D020866:omega-Conotoxin GVIA; D001920:Bradykinin; D002118:Calcium