Premium
The inhibitory effects of N 2 ‐dansyl‐ l ‐arginine‐4‐ t ‐butylpiperidine amide (TI 233) on contraction of vascular and intestinal smooth muscle
Author(s) -
Karaki H.,
Murakami K.,
Nakagawa H.,
Urakawa N.
Publication year - 1983
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1983.tb10724.x
Subject(s) - arginine , contraction (grammar) , muscle contraction , vascular smooth muscle , inhibitory postsynaptic potential , chemistry , smooth muscle , biochemistry , anatomy , endocrinology , biology , amino acid
1 Effects of N 2 ‐dansyl‐ l ‐arginine‐4‐ t ‐butylpiperidine amide (TI 233) on the contractions in vascular and intestinal smooth muscles were examined. 2 High K‐induced sustained contractions in the smooth muscles were inhibited by TI 233 with an IC 50 of 2.1 × 10 −5 m for rabbit aorta and 3.6 × 10 −6 m for guinea‐pig taenia coli in a solution containing 1.5 m m Ca. Initial transient contraction induced by K in taenia coli was less sensitive to the inhibitory effect of TI 233. When the Ca concentration in the medium was decreased to 0.3 m m , the concentration‐inhibition curves for TI 233 shifted to the left in both aorta and taenia coli. Increasing the Ca concentration to 7.5 m m shifted the curve to the right in the aorta. TI 233 also inhibited the noradrenaline‐induced contraction in the aorta (IC 50 = 2.1 × 10 −5 m ). 3 In a hypoxic solution without added glucose, the inhibitory effect of TI 233 on the K‐induced contraction in aorta was augmented. In the presence of high concentrations (40 m m ) of glucose in hypoxia, TI 233 did not inhibit the noradrenaline‐induced contraction of the aorta. Hypoxia and a high concentration of glucose also decreased the inhibitory effect of TI 233 on the K‐induced contraction in taenia coli. 4 TI 233 inhibited the K‐induced increase in cellular Ca content measured by a modified lanthanum method. 5 TI 233 decreased oxygen consumption and ATP content of resting and K‐stimulated aorta and taenia coli. 6 It was concluded that TI 233 inhibits the vascular and intestinal smooth muscle contraction by a Ca antagonistic action and also by inhibition of aerobic metabolism.