title: Interactions between angiotensin II and adenosine 3':5'-cyclic monophosphate in the regulation of amino acid transport by vascular smooth muscle cells.
abstract: The regulation of amino acid transport by angiotensin II (AII) and cyclic AMP (cAMP) was assessed in cultured vascular smooth muscle cells, using a nonmetabolizable amino acid, alpha-[3H]aminoisobutyric acid (AIB). An exposure time in excess of 2 h was required for AII to elicit a stimulatory response, the magnitude of which increased in a time-dependent manner for 12 h. AII-induced transport was blocked by [1-sarcosine, 8-isoleucine]AII, a competitive inhibitor of AII binding. The effect of AII was not abolished by downregulation protein kinase C with phorbol 12,13-dibutyrate or by use of a protein kinase C inhibitor, suggesting that transport in response to AII can be mediated by a protein kinase C independent pathway. In contrast, the elimination of calcium from the incubation medium reduced AII-stimulated AIB uptake. The calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide partially inhibited AIB uptake in response to AII, suggesting that calmodulin may be involved in the modulation of AII-stimulated amino acid transport. AIB transport was also increased by elevating intracellular cAMP levels via beta-adrenergic receptor stimulation, the use of a cAMP analog (N6-monobutyryl cAMP), or a phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine) or by direct stimulation of adenylate cyclase with forskolin. cAMP-induced AIB transport was evident within 10 min and peaked within 1 h. At 1 h AII enhanced cAMP-stimulated AIB transport. A possible mechanism for this effect is suggested by the observation that AII potentiated cAMP production in response to isoproterenol and 3-isobutyl-1-methylxanthine.
authors.affiliation: Department of Physiology, Marshall University School of Medicine, Huntington, WV 25755-9340, USA.
authors.forename: W D
authors.initials: WD
authors.lastname: McCumbee
authors.forename: V L
authors.initials: VL
authors.lastname: Hickey
authors.forename: L L
authors.initials: LL
authors.lastname: Lloyd
authors.forename: E I
authors.initials: EI
authors.lastname: Mangiarua
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000621:Aminoisobutyric Acids / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001692:Biological Transport; D000242:Cyclic AMP / Q000494:pharmacology*; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000621:Aminoisobutyric Acids; D010726:Phosphodiesterase Inhibitors; D000804:Angiotensin II; C100049:2-aminoisobutyric acid; D015240:Phorbol 12,13-Dibutyrate; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine