An amplifying effect of exogenous and neurally stored 5-hydroxytryptamine on the neurogenic contraction in rat tail...

1. The interactions between sympathetic neuroeffector transmission and 5-hydroxytryptamine (5-HT) were investigated in segments of rat isolated tail artery. 2. Contractile responses to field stimulation of the artery segments were abolished by tetrodotoxin (3 x 10(-7) M). A subthreshold concentration of acutely applied exogenous 5-HT (10(-8) M) markedly enhanced the contractions induced by sympathetic nerve stimulation, through an action on postjunctional 5-HT2-receptors. 3. The amplifying effect of 5-HT involved an enhanced influx of extracellular calcium into the smooth muscle cells. In contrast, the neurogenic contractions in vessels not exposed to 5-HT were not dependent on extracellular calcium. 4. The adrenergic component of the amplified response involved postjunctional alpha 1- but not alpha 2- adrenoceptor activation. 5. Exposure of the vessels to 5-HT (5 x 10(-7) M) for 30 min resulted in uptake of the amine into the perivascular sympathetic nerves, as demonstrated by immunohistochemistry. After chemical sympathectomy with 6-hydroxydopamine in vitro or in vivo, or surgical sympathectomy, there was little or no uptake. 6. Exposure to 5-HT followed by repeated washing resulted in an enhancement of the neurogenic contraction, which was still fully tetrodotoxin-sensitive. The enhanced response was blocked by ketanserin (10(-8) M) and prevented by the presence of the 5-HT uptake blocker, paroxetine (3 x 10(-8) M), during the period of exposure to 5-HT.