Effect of the thromboxane A2-mimetic U46619 on 5-HT1-like and 5-HT2 receptor-mediated contraction of the rabbit isolated femoral artery.
1. The influence of the thromboxane A2-mimetic U46619 (11 alpha, 9 alpha-epoxymethano PGH2) on 5-hydroxy-tryptamine (5-HT)-induced contractions of the rabbit isolated femoral artery has been examined. 2. In the absence of U46619, 5-HT responses were mediated predominantly by 5-HT2-receptors as judged by potent, surmountable antagonism by the selective 5-HT2 receptor antagonists, spiperone and ketanserin. Both antagonists unmasked a population of 5-HT1-like receptors which accounted for approximately 10-15% of the 5-HT maximum response. 3. In the presence of U46619 (3-10 nM), 5-HT-induced contractions were largely resistant to blockade by 5-HT2 receptor antagonists since 5-HT1-like receptor-mediated contraction now accounted for approximately 60% of the 5-HT maximum response. 4. These results show that activation of thromboxane A2 receptors in a tissue possessing both 5-HT2 and 5-HT1-like receptors can convert 5-HT-induced contraction from one mediated predominantly by 5-HT2 receptors to one which is mediated predominantly by 5-HT1-like receptors.
MacLennan
S J
SJ
Analytical Pharmacology Group, Wellcome Research Laboratories, Beckenham, Kent.
Martin
G R
GR
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects*
D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D011985:Receptors, Serotonin; D012701:Serotonin; D013134:Spiperone; D013928:Thromboxane A2; D007650:Ketanserin; C060013:vapiprost