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Inhibition of tracheal smooth muscle contraction and myosin phosphorylation by ryanodine

Journal Article · · J. Pharmacol. Exp. Ther.; (United States)
OSTI ID:6805362
; ;

Previous studies have shown that muscarinic activation of airway smooth muscle in low Ca++ solutions increases myosin phosphorylation without increasing tension. Blocking Ca++ influx reduced phosphorylation, but not to basal levels. It was proposed that release of intracellular Ca++ contributed to dissociation of phosphorylation and contraction. To test this hypothesis the effects of ryanodine were studied under similar conditions. Ryanodine (10(-7) to 10(-5) M) antagonized caffeine-induced contraction of canine tracheal smooth muscle. Ryanodine also reduced carbachol-induced contractions and carbachol-induced myosin phosphorylation. The effect of ryanodine on potassium and serotonin-induced contractions was also investigated to test for a nonspecific inhibitory effect. In contrast to the effect on carbachol responses, ryanodine (10(-5) M) potentiated the contractile response to low concentrations of serotonin and potassium, but had no effect on the maximum response to either stimulant. Carbachol (10(-6) M) and ryanodine (10(-5) M) both significantly decreased /sup 45/Ca++ content of tracheal muscle. The effect of ryanodine and carbachol together on /sup 45/Ca++ content was not greater than either drug alone suggesting that ryanodine reduces the caffeine and carbachol responses by depleting releaseable Ca++ stores. Ryanodine significantly reduced Ca++-induced contraction and myosin phosphorylation in carbachol-stimulated muscle, suggesting that some of the Ca++ responsible for elevated phosphorylation is released from the sarcoplasmic reticulum.

Research Organization:
Univ. of Nevada School of Medicine, Reno (USA)
OSTI ID:
6805362
Journal Information:
J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 246:2; ISSN JPETA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METALS
ALKALOIDS
ANALEPTICS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
CAFFEINE
CALCIUM
CALCIUM 45
CALCIUM ISOTOPES
CENTRAL NERVOUS SYSTEM AGENTS
CHEMICAL REACTIONS
CONTRACTION
DAYS LIVING RADIOISOTOPES
DOGS
DRUGS
ELEMENTS
EVEN-ODD NUCLEI
GLOBULINS
HETEROCYCLIC COMPOUNDS
IN VITRO
INHIBITION
INSECTICIDES
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
METALS
MUSCLES
MYOSIN
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PARASYMPATHOMIMETICS
PESTICIDES
PHOSPHORYLATION
PROTEINS
PURINES
RADIOISOTOPES
RESPIRATORY SYSTEM
SECRETION
TRACER TECHNIQUES
TRACHEA
VERTEBRATES
XANTHINES