Amplification of 5-hydroxytryptamine-induced contractile responses via 5-hydroxytryptamine receptors and alpha-adrenoceptors in dog mesenteric artery and vein.
The interactions between 5-hydroxytryptamine (5-HT) and both serotonergic and alpha adrenoceptors were investigated by using isolated dog mesenteric vascular rings mounted in tissue baths for the measurement of isometric contraction. In the mesenteric artery, 5-HT elicited concentration-dependent contractions, producing 46.5% of the KCl maximal response. At low concentrations, the 5-HT-induced contraction was effectively inhibited by 10(-6) M methysergide and by 10(-6) M ketanserin, but was prazosin-resistant. At high 5-HT concentrations, the contractile response was effectively antagonized by 10(-7) M prazosin. The presence in the medium of 20 mM KCl, which increased resting tension less than 10% of the KCl maximal response, markedly enhanced the responses to 5-HT primarily at concentrations lower than 10(-5) M. These amplified responses were methysergide-sensitive, but prazosin- and ketanserin-resistant. In the mesenteric vein, exposure to 5-HT caused an extremely small contraction, producing 5.2 +/- 4.3% of the KCl maximal response. In the presence of 20 mM KCl, which had small contractile effects, 5-HT produced a biphasic concentration-response curve. Methysergide (10(-6) M) and 10(-6) M ketanserin effectively inhibited the responses to low concentrations of 5-HT, and only 10(-7) M rauwolscine effectively blocked the responses to high concentrations of 5-HT. In the dog mesenteric artery, our data suggest that addition of threshold concentrations of KCl enhanced the contractile response to 5-HT through amplification of 5-HT1-like receptor-mediated responses. In the dog mesenteric vein, KCl enhanced 5-HT responses via amplification of both 5-HT2 receptor- and alpha-2 adrenoceptor-mediated responses.
Shimamoto
H
H
Department of Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Shimamoto
Y
Y
Kwan
C Y
CY
Daniel
E E
EE
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D008642:Mesenteric Veins / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D011189:Potassium Chloride