title: Role of sarcoplasmic reticulum in the myorelaxant activity of nitric oxide donors in guinea pig gastric fundus.
abstract: 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.
authors.affiliation: Institute of Biophysics, Bulgarian Academy of Sciences, Sofia. gpetkov@unisi.it
authors.forename: G V
authors.initials: GV
authors.lastname: Petkov
authors.forename: G D
authors.initials: GD
authors.lastname: Spassov
authors.forename: K K
authors.initials: KK
authors.lastname: Boev
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005748:Gastric Fundus / Q000187:drug effects / Q000648:ultrastructure; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D026902:Potassium Channel Blockers; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000502:physiology; D019284:Thapsigargin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D007476:Ionophores; D020030:Nitric Oxide Donors; D026902:Potassium Channel Blockers; D019831:Sodium-Calcium Exchanger; D014665:Vasodilator Agents; D009599:Nitroprusside; D000001:Calcimycin; C002385:linsidomine; D019284:Thapsigargin; D008981:Molsidomine; D000109:Acetylcholine; D002118:Calcium; C000543:cyclopiazonic acid