Petkov G V, Spassov G D, Boev K K
Institute of Biophysics, Bulgarian Academy of Sciences, Sofia.
Eur J Pharmacol. 1998 Jul 31;354(1):59-66. doi: 10.1016/s0014-2999(98)00438-5.
The relaxant effect of two nitric oxide (NO) donors: sodium nitroprusside and 3-morpholino-sydnonimine (SIN-1) on circular smooth muscle strips isolated from guinea pig gastric fundus was studied with the view to elucidating the mechanism, which underlies the NO-induced relaxation of this tissue. Both sodium nitroprusside (10(-9)-10(-5) M) and SIN-1 (10(-9)-10(-4) M) suppressed the spontaneous fundus tone and hyperpolarized the muscle cells by about 5 mV. They antagonized the acetylcholine (10(-6) M)-induced tone and exerted their relaxant effects even when Ca2+ influx into the cells was triggered through the Na+/Ca2+ exchanger. Sodium nitroprusside and SIN-1 antagonized the contraction induced by cyclopiazonic acid (10(-5) M), a specific inhibitor of the sarcoplasmic reticulum Ca2+-ATPase. In the presence of high concentrations of sodium nitroprusside or SIN-1, cyclopiazonic acid (10(-5) M) exerted only a slight if any contractile effect. After the complete relaxation induced by sodium nitroprusside or SIN-1, the K+-channel blockers, tetraethylammonium, apamin and charybdotoxin, as well as the Ca2+ ionophore, A 23187, induced high-amplitude contractions, suggesting that the Ca2+ sensitivity of the contractile myofilaments was not affected. The results suggest that NO, released from NO donors increases the sarcoplasmic reticulum Ca2+ uptake thereby enhancing the vectorial sarcoplasmic reticulum Ca2+ release toward the plasmalemma to elicit membrane hyperpolarization and relaxation in guinea pig gastric fundus.
研究了两种一氧化氮（NO）供体硝普钠和3-吗啉代西多尼明（SIN-1）对从豚鼠胃底分离的环形平滑肌条的舒张作用，旨在阐明NO诱导该组织舒张的机制。硝普钠（10^(-9)-10^(-5) M）和SIN-1（10^(-9)-10^(-4) M）均抑制胃底的自发张力，并使肌细胞超极化约5 mV。它们拮抗乙酰胆碱（10^(-6) M）诱导的张力，即使通过Na+/Ca2+交换体触发Ca2+流入细胞时也能发挥舒张作用。硝普钠和SIN-1拮抗由环匹阿尼酸（10^(-5) M）诱导的收缩，环匹阿尼酸是肌浆网Ca2+-ATP酶的特异性抑制剂。在高浓度硝普钠或SIN-1存在下，环匹阿尼酸（10^(-5) M）即使有收缩作用也很轻微。在硝普钠或SIN-1诱导完全舒张后，K+通道阻滞剂四乙铵、蜂毒明肽和大蝎毒素以及Ca2+离子载体A 23187诱导高幅度收缩，这表明收缩性肌丝的Ca2+敏感性未受影响。结果表明，从NO供体释放的NO增加了肌浆网Ca2+摄取，从而增强了肌浆网向质膜的矢量Ca2+释放，引起豚鼠胃底膜超极化和舒张。
