Effects of [Sar1]angiotensin II on proenkephalin gene expression and secretion of [Met5]enkephalin in bovine adrenal medullary chromaffin cells.
We have studied the effect of [Sar1]angiotensin II [S1-AII; a degradation-resistant analogue of angiotensin II (AII) on the release of [Met5]enkephalin (ME) and proenkephalin A (proENK) gene expression. Short-term (15-min to 1-h) stimulation of bovine adrenal medullary chromaffin (BAMC) cells with S1-AII at concentrations from 0.1 to 100 nM had no significant effect on secretion of ME, whereas high concentrations of S1-AII (3 to 100 microM) produced a concentration-dependent increase in the concentration of ME in the incubation media. In contrast, long-term (3- to 24-h) stimulation with low concentrations (0.1 nM-1 microM) of S1-AII increased the secretion of ME in a concentration-dependent manner (EC50 = 1 nM). The intracellular level of ME was not changed by long-term treatment with S1-AII (100 nM). In addition to increased ME secretion, long-term (24-h) stimulation with S1-AII increased the expression of proENK mRNA in a concentration-dependent manner (EC50 = 4 nM). Losartan (2-n-butyl-4 chloro-5-hydroxymethyl-1-[(2'-(1 H-tetrazol-5-yl)biphenyl-4-yl)- methyl]imidazole potassium salt, a type 1 AII receptor antagonist) inhibited these effects, whereas PD123319 (50 microM, a type 2 AII receptor antagonist) was inactive. Our results suggest that AII in BAMC cells exerts a major effect on the long-term regulation of expression of proENK mRNA and secretion of ME. These effects appear to be mediated by type 1-like AII receptors.
Suh
H H
HH
Section of Neuropharmacology, National Institute of Environmental Health Science, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Mar
E C
EC
Hudson
P M
PM
McMillian
M K
MK
Hong
J S
JS
D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000378:metabolism*; D004745:Enkephalins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000235:genetics*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism
D004745:Enkephalins; D007093:Imidazoles; D015335:Molecular Probes; D011498:Protein Precursors; D011725:Pyridines; D012333:RNA, Messenger; C029992:proenkephalin; D000804:Angiotensin II; C073402:PD 123319; D004744:Enkephalin, Methionine; C074793:angiotensin II, Sar(1)-