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KMID : 0360419940300010101
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Korean Journal of Pharmacology
1994 Volume.30 No. 1 p.101 ~ p.109
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Mechanisms Underlying the Inhibitory Effect of GS 283 in Various Smooth Muscles
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Kim Si-Hwan
Lee Young-Soo
Chong Won-Seog
Chang Ki-Churl
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Abstract
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Pharmacological characterization of GS 283, a tetrahydroisoquinoline derivative has been elucidated using rat thoracic aorta, guinea pig tenea coli and rabbit mesentery artery in vitro. GS 283 showed calcium antagonistic action in vascular smooth muscle, since high contraction was concentration dependently inhibited. GS 283 also inhibited the contraction induced by receptor activation. Vasodilating action of GS 283 was not modified by the propranolol, indicating that GS 283 has no receptor stimulatory action. Simultaneous measurement of intracellular calcium change and muscle tension indicated that the inhibitory effect of GS 283 was accompanied by the increase in tissue fluorescence. This increment was not due to fura 2 fluorescence but to endogenous pyridine nucleotide, suggesting that GS 283 has an effect to inhibit mitochondrial function. GS 283 had an inhibitory action on cyclic AMP and GMP-dependent phosphodiesterases from rat brain with Ki values of 2.5 and 6.7 mM. From these findings we concluded that GS 283 has multiple action such as the inhibition of cyclic nucleotide-dependent phosphodiesterases, blocking of calcium channel as well as inhibition of mitochondrial function which are responsible for vasodilatation.
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KEYWORD
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Calcium channel, Smooth muscle, Phosphodiesterase inhibitor
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