Author:
Secondo Agnese,Pannaccione Anna,Cataldi Mauro,Sirabella Rossana,Formisano Luigi,Di Renzo Gianfranco,Annunziato Lucio
Abstract
The role of nitric oxide (NO) in the occurrence of intracellular Ca2+concentration ([Ca2+]i) oscillations in pituitary GH3cells was evaluated by studying the effect of increasing or decreasing endogenous NO synthesis with l-arginine and nitro-l-arginine methyl ester (l-NAME), respectively. When NO synthesis was blocked with l-NAME (1 mM) [Ca2+]i, oscillations disappeared in 68% of spontaneously active cells, whereas 41% of the quiescent cells showed [Ca2+]ioscillations in response to the NO synthase (NOS) substrate l-arginine (10 mM). This effect was reproduced by the NO donors NOC-18 and S-nitroso- N-acetylpenicillamine (SNAP). NOC-18 was ineffective in the presence of the L-type voltage-dependent Ca2+channels (VDCC) blocker nimodipine (1 μM) or in Ca2+-free medium. Conversely, its effect was preserved when Ca2+release from intracellular Ca2+stores was inhibited either with the ryanodine-receptor blocker ryanodine (500 μM) or with the inositol 1,4,5-trisphosphate receptor blocker xestospongin C (3 μM). These results suggest that NO induces the appearance of [Ca2+]ioscillations by determining Ca2+influx. Patch-clamp experiments excluded that NO acted directly on VDCC but suggested that NO determined membrane depolarization because of the inhibition of voltage-gated K+channels. NOC-18 and SNAP caused a decrease in the amplitude of slow-inactivating ( IDR) and ether-à-go-go-related gene ( ERG) hyperpolarization-evoked, deactivating K+currents. Similar results were obtained when GH3cells were treated with l-arginine. The present study suggests that in GH3cells, endogenous NO plays a permissive role for the occurrence of spontaneous [Ca2+]ioscillations through an inhibitory effect on IDRand on IERG.
Publisher
American Physiological Society
Cited by
24 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献