[The mechanism of ergonovine-induced airway smooth muscle contraction].
There have been three articles in the clinical literature concerning ergonovine maleate-induced bronchospasm. The effect of this alkaloid on isolated canine tracheobronchial smooth muscle was analyzed to investigate the mechanism of ergonovine-induced airway smooth muscle contraction. Both ergonovine and serotonin (5-hydroxytryptamine, 5HT) contracted canine tracheal smooth muscle with EC50 1.4 X 10(-8) M and 5.1 X 10(-7) M, respectively. The maximal contractile response observed with ergonovine was approximately 30% less than that observed with 5HT. In diverse blockers such as methysergide, atropine, prazosin, propranolol, pyrilamine and cimetidine, only methysergide competitively blocked both ergonovine and 5HT responses with a similar calculated dissociation constant (pKB); 8.3 +/- 0.2 against ergonovine and 8.5 +/- 0.2 against 5HT (n = 6, p = 0.9). The relative affinity and efficacy of ergonovine and 5HT were determined by use of a partial irreversible antagonist, phenoxybenzamine. The calculated affinity of ergonovine was about 16 times higher than that of 5HT. The relative efficacy of EC100 for ergonovine was 0.2 but at EC10 it was 41.9 (5HT efficacy = 1). Ergonovine 10(-9) M or 10(-8) M shifted the 5HT dose-response curve to the right without reducing the maximal response, but the shift was nonparallel. Ergonovine and 5HT also contracted canine bronchial smooth muscle in a dose dependent manner with EC50 6.4 X 10(-8) M and 1.8 X 10(-7) M, respectively. The dose-responses curve of these two agonists were competitively blocked by methysergide 10(-6) M. These data indicate that ergonovine directly contracts canine tracheobronchial smooth muscle as a result of its combination with 5HT receptors. This effect may result in the precipitation of an asthmatic attack in susceptible individuals.
Sakamoto
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Y
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004874:Ergonovine / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D004874:Ergonovine; D008784:Methysergide