RT Journal Article
SR Electronic
T1 Mechanism by which serotonin attenuates contractile response of canine mesenteric arterial smooth muscle.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 322
OP 329
VO 232
IS 2
A1 Moreland, R S
A1 van Breemen, C
A1 Bohr, D F
YR 1985
UL http://jpet.aspetjournals.org/content/232/2/322.abstract
AB 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.