Role of ryanodine receptors in chloroform-induced contraction in Swine tracheal smooth muscle.
Chloroform has been reported to induce inhalation intoxication in the respiratory tract. The purpose of this study was to investigate the effects and mechanisms of chloroform on muscle contraction in isolated swine tracheal smooth muscle. Chloroform (30-1000 ppm) reversibly and concentration-dependently provoked smooth muscle contraction. Muscarinic and alpha-adrenergic receptor antagonists did not alter chloroform-induced muscle contraction, indicating muscarinic and alpha-adrenergic stimulation may not be involved in chloroform-induced responses. Caffeine (10 mM) was observed to directly evoke tracheal smooth muscle contraction, but ryanodine (1 microM) was not. However, ryanodine and caffeine abolished chloroform-induced smooth muscle contraction by 80.0 +/- 8.0 and 79.6 +/- 6.0%, respectively. Caffeine combined with ryanodine completely blocked chloroform-induced contractile responses. Thus, it suggests that chloroform released Ca(2+) from ryanodine-sensitive internal Ca(2+) pools. Although short-term removal of Ca(2+) from extracellular environment slightly decreased chloroform-induced contractile responses, L-type Ca(2+) channel blockers did not alter tracheal smooth muscle contraction induced by chloroform. Collectively, our results indicated that chloroform directly and concentration-dependently provoked muscle contraction in swine tracheal smooth muscle, which may result from the activation of ryanodine receptor Ca(2+) release channel in sarcoplasmic reticulum but may not depend on muscarinic and adrenergic activation and Ca(2+) entry from the extracellular environment.
Lin
Yi-Ruu
YR
Institute of Pharmacology and Toxicology, Tzu Chi University, No 701, Section 3, Chung Yang Road, Hualien 970, Taiwan.
Chen
Hwei-Hsien
HH
Chan
Ming-Huan
MH
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D002725:Chloroform / Q000494:pharmacology*; D018678:Cholinergic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*; D013552:Swine; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D018663:Adrenergic Agents; D018678:Cholinergic Agents; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D019837:Ryanodine Receptor Calcium Release Channel; D002725:Chloroform