Involvement of Ca2+ mobilization in the amplifying effect of serotonin on responses of rabbit isolated ear artery to exogenous noradrenaline.
The present study examined the involvement of Ca2+ mobilization in the amplifying effect of serotonin on steady-state responses of rabbit isolated perfused ear artery to exogenous noradrenaline (NA; 0.001-3 mumol/l). In contrast to its marked amplifying effect on responses to NA, serotonin in the subconstrictor concentration of 100 nmol/l had no effect on responses to KCl. The Ca2+-entry blocking drug diltiazem (10 mumol/l) decreased responses to NA; in addition, the amplifying effect of serotonin on responses to NA was reduced by diltiazem. Lowering the concentration of Ca2+ in the Krebs-Henseleit perfusion solution from 2.5 to 0.25 mmol/l also reduced both responses to NA and the amplifying effect of serotonin. Using the method of Manzini et al. (1982), separate intra- and extracellular Ca2+-dependent responses to NA were obtained. Serotonin had no effect on intracellular Ca2+-dependent responses to NA but enhanced extracellular Ca2+-dependent NA responses. These results suggest that the amplifying effect of serotonin on responses of rabbit ear artery to exogenous NA involves a selective enhancement of the component of the NA response which is dependent on extracellular Ca2+; serotonin may increase NA-evoked entry of Ca2+ into the vascular smooth muscle cells through receptor-operated Ca2+ channels.
Meehan
A G
AG
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Medgett
I C
IC
Story
D F
DF
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology*
D012701:Serotonin; D011189:Potassium Chloride; D004110:Diltiazem; D002118:Calcium; D009638:Norepinephrine