Mechanism by which serotonin attenuates contractile response of canine mesenteric arterial smooth muscle.
We investigated the mechanism by which prior exposure to serotonin (5-HT) attenuates contractile response to norepinephrine (NE) in dog mesenteric artery. Helically cut strips from dog mesenteric artery were mounted in muscle baths for isometric force recording. Prior treatment with 5-HT (10(-8) to 2 X 10(-7) M) attenuated the response to 2.5 X 10(-7) M NE by 26 to 61%. The attenuation lasted approximately 30 min. The attenuation is not affected by adrenergic denervation, endothelial removal, propranolol, indomethacin or arachidonate. Prior treatment with 5-HT also attenuated responses to: methoxamine, clonidine, prostaglandin F2 alpha, KCl and 5-HT itself. Inhibition of sodium influx by amiloride or inhibition of the electrogenic pump by ouabain diminished the NE attenuation. Verapamil, a calcium channel blocker, diminished the attenuation by 5-HT whereas ryanodine, an intracellular calcium release blocker, had no effect. Prior treatment with 5-HT caused a reduction in the 45Ca influx stimulated by NE. Ketanserin, a 5-HT blocker, exaggerated the attenuation of the NE response caused by 5-HT. Methysergide and cyproheptadine, also 5-HT blockers, diminished the attenuation. These results are compatible with the following interpretation: 1) 5-HT attenuates both receptor- and nonreceptor-mediated contractions of vascular smooth muscle; 2) this attenuation is the result of an increased sodium influx that stimulates the electrogenic sodium pump to cause membrane hyperpolarization and decreased stimulated calcium influx; and 3) the effects of 5-HT are mediated by 5-HT receptors that are blocked by methysergide and cyproheptadine but not by ketanserin.
Moreland
R S
RS
van Breemen
C
C
Bohr
D F
DF
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism
D007473:Ion Channels; D012702:Serotonin Antagonists; D012701:Serotonin; D012964:Sodium; D002118:Calcium; D009638:Norepinephrine