Parthenolide inhibits the contractile responses of rat stomach fundus to fenfluramine and dextroamphetamine but not serotonin.
The isolated rat stomach fundus preparation, a sensitive bioassay to evaluate serotonin-(5-HT) like activity, was used as a model to study the effects of parthenolide (PAR), a component to Tanacetum parthenium (feverfew), on 5-HT storage, release and stimulation of the 5-HT2B receptor. Cumulative-concentration response curves to 5-HT and the indirect-acting serotonergics fenfluramine (F) and dextroamphetamine (DA) on fundus were obtained in the presence and absence of 1 x 10(-6) to 1 x 10(-5) PAR. 5-HT release elicited by F and DA was indirectly assessed by comparing the contraction elicited by these compounds on tissues from reserpine-treated, L-p-chlorophenylalanine (l-PCPA)-treated and untreated rats. The observed order of agonist potencies on intact fundus was: 5-HT > DA > F and the order of intrinsic activity was: 5-HT > DA > F. PAR did not show agonist effects nor antagonism toward 5-HT on rat fundus at all concentrations used. However, PAR antagonized non-competitively the effects of F and DA. Contractile responses to 5-HT were not significantly different on mucosa-denuded fundus and tissue strips from untreated, l-PCPA- and reserpine-treated rats. PAR appears to inhibit 5-HT release mediated responses by the indirect-acting 5-HT agonists on fundal tissue.
Béjar
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Research Institute of Pharmaceutical Sciences, University of Mississippi, University 38677, USA.
D000818:Animals; D003913:Dextroamphetamine / Q000494:pharmacology*; D005277:Fenfluramine / Q000494:pharmacology*; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D010946:Plants, Medicinal; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology*
D018490:Serotonin Agents; D012702:Serotonin Antagonists; D012717:Sesquiterpenes; D005277:Fenfluramine; C002669:parthenolide; D012701:Serotonin; D003913:Dextroamphetamine; D011224:Prazosin