Effect of alpha adrenergic agonist on the rabbit ear artery contraction to serotonin: enhanced response mediated by serotonergic1-like receptors.
The effect of methoxamine or phenylephrine (PHE) on the contractile response of the rabbit ear artery to serotonin was assessed by using isolated arterial rings mounted in tissue baths for the measurement of isometric force development. A contractile threshold concentration of methoxamine or PHE (10-30 nM) shifted the serotonin concentration-response curve to the left by approximately 200-fold. Neither mechanical removal of the vascular endothelium nor chemical denervation had any effect on the alpha agonist-amplified response of ear artery to serotonin. Although the response to serotonin in the absence of the alpha agonist was mediated primarily by alpha-1 adrenergic receptors, prazosin did not block the amplified response to serotonin. Ketanserin (10 nM), ritanserin (50 nM) and MDL 72222 (1 microM) also had no effect on the amplified response, ruling out the involvement of serotonergic (5-HT)2 and 5-HT3 receptors. However, methiothepin (3 nM) and 1-(1-naphthyl)piperazine (10 and 100 nM) blocked the PHE-amplified contraction of ear artery to serotonin. When the contractile response of ear artery to 5-carboxamidotryptamine was measured in the presence of a threshold concentration of alpha agonist, the concentration-response curve was shifted 8300-fold to the left. The amplified response to 5-carboxyamidotryptamine was insensitive to 10 nM ketanserin, but was blocked by 3 nM methiothepin. Sumatriptan, a selective 5-HT1 agonist, failed to induce vasoconstriction in the absence of a threshold concentration of alpha agonist. However, in the presence of PHE, sumatriptan induced a concentration-dependent contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Movahedi
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Department of Pharmacology, College of Medicine, University of California, Irvine.
Le
H T
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Spanggord
H M
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Purdy
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D000818:Animals; D004357:Drug Synergism; D004423:Ear / Q000098:blood supply; D008297:Male; D008729:Methoxamine / Q000008:administration & dosage; D010656:Phenylephrine / Q000008:administration & dosage; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000008:administration & dosage*; D014661:Vasoconstriction / Q000187:drug effects*; D014666:Vasomotor System / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D010656:Phenylephrine; D012701:Serotonin; D008729:Methoxamine