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KMID : 0390119950350020075
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Journal of Pusan Medical College
1995 Volume.35 No. 2 p.75 ~ p.88
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A Study on Muscarinic Receptors and Calcium Utilization in Acetylcholic-induced Contraction of Porcine Coronary Artery
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Abstract
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In the present study it was aimed to investigate which subtypes of muscarinic receptors are involved in the contraction of the procine coronary artery by comparing the affinities of several muscarinic antagonists: (nonspectific antagonist),
pirenzepine(M1 antagonist), methoctramine (M2 antagonist) and hexahydroxyl-sila-difenidol p-fluoro alaog(pE-HHSiD). Furthermore, the relationships between the sources of Ca2+ for contration and the activation of muscarinic receptors were
examined.
1. Acetylcholine contracted porcine coronary artery in a dose-dependent manner and EC50 was 3.92±0.62×10-7 M. Acetylcholine-induced contraction was little little affected by incubation in Ca2+ -free medium containing 1mM EGTA. However the
contractile
response to acetylcholine was significantly inhibited by trifluoperazine, a calmodulin antagonist. The incubation with pertussis toxin(50ng/㎖up to 4 hours) did not affect the acetylcholine-induced contraction.
2. Pretreatment with muscarinic antagonists caused a parallel rightward shift of the concentration-response curves of acetylcholine. The order of affinity of the antagonists in muscarinic receptors in porcine coronary artery was derived:
atropine>pFHHSiD>pirenzepint>methoctramine. None of the slopes of Schild plots was significantly difference from the unity.
3. Acetylcholine dose-dependently produced a phasic increase in [Ca2+] I followed by a tonic increase which was not affected in Ca2+-free medium. In skinned strips of porcine coronary artery GTPrS(100μM) increased [Ca2+]I which greatly
inhibited
by
GDPS.
4. Pirenzepine and pF-HHSiD but not methoctramine greatly inhibited the increase in [Ca2+]I induced by acetylcholine. The order of potency of antagonists to inhibit the increase in [Ca2+]I induced by acetylcholine was pirenzepine+PF-HHSiP>
methoctramine.
Taken together, it is concluded that acetylcholine-induced contraction of porcine coronary artery is mediated by the Ca2+ released from intracellular storage sites and the activation of muscarinic receptors mainly belonged to M1 and M3 receptor
subtypes, which are coupled with a pertussis toxin-insensitive G-proteins.
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