Yanagihara N, Okazaki M, Terao T, Uezono Y, Wada A, Izumi F
Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1991 Mar;343(3):289-95. doi: 10.1007/BF00251128.
We studied the effect of brain natriuretic peptide (BNP) on the accumulation of cyclic GMP and the phosphorylation and activity of tyrosine hydroxylase, compared with that of atrial natriuretic peptide (ANP), in cultured bovine adrenal medullary cells. 1. BNP as well as ANP increased cellular cyclic GMP accumulation in a concentration-dependent manner (10-1000 nmol/l). BNP (1 mumol/l) and ANP (1 mumol/l) produced a 60-fold and 30-fold increase in cyclic GMP accumulation, respectively. 2. The stimulatory effects of BNP and ANP on cyclic GMP accumulation were observed even when Ca2+ or Na+ was removed from the incubation medium. 3. 12-O-Tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C, inhibited the stimulatory effect of BNP on cyclic GMP accumulation in a concentration-dependent manner (1-100 nmol/l). Furthermore, the BNP-induced accumulation of cyclic GMP was attenuated by forskolin (1 mumol/l), an activator of adenylate cyclase. 4. BNP (1 mumol/l) and ANP (1 mumol/l) caused a significant increase in phosphorylation and activity of tyrosine hydroxylase in the cells. 5. In digitonin-permeabilized cells, cyclic GMP (1-100 mumol/l) activated tyrosine hydroxylase in the presence of ATP and Mg2+. These results suggest that BNP stimulates the accumulation of cyclic GMP in a manner similar to that of ANP. The increased accumulation of cyclic GMP by these peptides may be negatively modulated by protein kinase C and cyclic AMP and may cause the phosphorylation and activation of tyrosine hydroxylase in cultured bovine adrenal medullary cells.
我们在培养的牛肾上腺髓质细胞中，研究了脑钠肽（BNP）对环磷酸鸟苷（cGMP）积累以及酪氨酸羟化酶磷酸化和活性的影响，并与心房钠尿肽（ANP）进行了比较。1. BNP和ANP均以浓度依赖性方式（10 - 1000 nmol/L）增加细胞内cGMP的积累。BNP（1 μmol/L）和ANP（1 μmol/L）分别使cGMP积累增加60倍和30倍。2. 即使从孵育培养基中去除Ca2+或Na+，也能观察到BNP和ANP对cGMP积累的刺激作用。3. 蛋白激酶C激活剂12 - O - 十四烷酰佛波醇13 - 乙酸酯（TPA）以浓度依赖性方式（1 - 100 nmol/L）抑制BNP对cGMP积累的刺激作用。此外，腺苷酸环化酶激活剂福斯可林（1 μmol/L）可减弱BNP诱导的cGMP积累。4. BNP（1 μmol/L）和ANP（1 μmol/L）使细胞中酪氨酸羟化酶的磷酸化和活性显著增加。5. 在洋地黄皂苷透化的细胞中，cGMP（1 - 100 μmol/L）在ATP和Mg2+存在的情况下激活酪氨酸羟化酶。这些结果表明，BNP以类似于ANP的方式刺激cGMP的积累。这些肽类导致的cGMP积累增加可能受到蛋白激酶C和环磷酸腺苷（cAMP）的负调节，并可能导致培养的牛肾上腺髓质细胞中酪氨酸羟化酶的磷酸化和激活。
