PMID- 2539754 OWN - NLM STAT- MEDLINE DCOM- 19890512 LR - 20171213 IS - 0002-9513 (Print) IS - 0002-9513 (Linking) VI - 256 IP - 4 Pt 2 DP - 1989 Apr TI - Beta-receptor-adenylate cyclase coupling in hypoxic neonatal rat ventricular myocytes. PG - H1209-17 AB - This study investigated the influence of hypoxia on alterations in the beta-adrenergic receptor-adenylate cyclase system. Cultured neonatal rat ventricular myocytes were subjected to normoxia (incubator PO2 135-145 mmHg) or hypoxia (incubator PO2 0-14 mmHg) and, in crude membrane preparations, beta-receptor binding properties were measured with [125I]iodocyanopindolol and adenylate cyclase activity by radioimmunoassay. Hypoxia of 30 min in duration caused no alteration in beta-receptor density (Bmax 75 +/- 11 vs. 71 +/- 12 fmol/mg protein) but increased adenylate cyclase activity under basal conditions and during stimulation with l-isoproterenol, 5'-guanylimidotriphosphate [Gpp(NH)p] 5 X 10(-5) M, NaF 10(-4) M, and forskolin 10(-4) M. For example, isoproterenol 10(-5) M + guanosine 5'-triphosphate (GTP) 5 X 10(-5) M gave 221 +/- 34 vs. 143 +/- 11 pmol.min-1.mg protein-1, P less than 0.05 hypoxia vs. normoxia. After 60 min of hypoxia, adenylate cyclase activity was no longer increased. Hypoxia of 120-150 min duration increased Bmax by 64% (73 +/- 8 to 120 +/- 11 fmol/mg protein, P less than 0.05 vs. normoxia) but decreased adenylate cyclase activity during stimulation with isoproterenol, NaF 10(-4) M, and forskolin 10(-4) M. For example, isoproterenol 10(-5) M + GTP 5 X 10(-5) M gave 107 +/- 12 vs. 148 +/- 11 pmol.min-1.mg protein-1, P less than 0.05 hypoxia vs. normoxia. Reoxygenation for 15 min following 120-150 min of hypoxia reversed the increased beta-receptor numbers and decreased adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS) FAU - Thandroyen, F T AU - Thandroyen FT AD - Department of Internal Medicine (Cardiology), University of Texas, Southwestern Medical Center, Dallas 75235. FAU - Muntz, K AU - Muntz K FAU - Rosenbaum, T AU - Rosenbaum T FAU - Ziman, B AU - Ziman B FAU - Willerson, J T AU - Willerson JT FAU - Buja, L M AU - Buja LM LA - eng GR - HL-17669/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Physiol JT - The American journal of physiology JID - 0370511 RN - 0 (Receptors, Adrenergic, beta) RN - EC 4.6.1.1 (Adenylyl Cyclases) RN - S88TT14065 (Oxygen) SB - IM MH - Adenylyl Cyclases/*metabolism MH - Animals MH - Cells, Cultured MH - Coronary Disease/metabolism MH - In Vitro Techniques MH - Myocardium/*metabolism MH - Oxygen/*physiology MH - Rats MH - Receptors, Adrenergic, beta/*metabolism MH - Time Factors EDAT- 1989/04/01 00:00 MHDA- 1989/04/01 00:01 CRDT- 1989/04/01 00:00 PHST- 1989/04/01 00:00 [pubmed] PHST- 1989/04/01 00:01 [medline] PHST- 1989/04/01 00:00 [entrez] AID - 10.1152/ajpheart.1989.256.4.H1209 [doi] PST - ppublish SO - Am J Physiol. 1989 Apr;256(4 Pt 2):H1209-17. doi: 10.1152/ajpheart.1989.256.4.H1209.