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DJ Cushing and ML Cohen
Cardiovascular Research, Lilly Research Laboratories Eli Lilly and Company, Indianapolis, Indiana.
Serotonin (5-HT) is one important mediator of the coronary vasospasm and occlusion associated with thrombosis and atherosclerosis. 5-HT concentration-dependently contracted both canine and porcine coronary artery rings in vitro. In the dog, 5-HT-induced contraction was not blocked by either LY53857 (1 microM) or ketanserin (1 microM), but was blocked by the nonselective 5-HT receptor antagonist 1- naphthylpiperazine (1-NP) (100 nM), indicating 5-HT receptor involvement. Unlike the dog, both LY53857 (1 microM) and ketanserin (30 nM) antagonized 5-HT-induced contraction in pig arteries. Dissociation constants for LY53857 and ketanserin in porcine arteries were compared with those in rat jugular vein, a tissue possessing a well characterized 5-HT2 receptor. Both LY53857 (3 nM) and ketanserin (3 nM) antagonized 5-HT-induced contraction in rat jugular vein; however, the affinities of LY53857 and ketanserin in the rat jugular vein were significantly higher than those in the pig coronary. The rank order contractile potency for 5-HT, (alpha Me-5-HT) and sumatriptan in porcine coronary artery was consistent with that established for a 5- HT2 receptor, whereas the rank order potency in canine coronary artery indicated non-5-HT2 receptor involvement. Sumatriptan, a 5-HT1D receptor-selective agonist, was equieffective to 5-HT in contracting the canine coronary artery, a response inhibited by 1-NP (100 nM). Sumatriptan failed to contract either the pig coronary or rat jugular vein. In summary, significant differences exist in the 5-HT receptors that mediate contraction between the canine and porcine coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)
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