Rapid intracellular release of calcium in human platelets by stimulation of 5-HT2-receptors.

The concentration of intracellular free Ca2+ ( [Ca2+]i) in human blood platelets was measured by use of the fluorescent probe quin-2. 5-Hydroxytryptamine (5-HT) caused a rapid increase of [Ca2+]i in the presence or absence of Ca2+ in the medium. The [Ca2+]i-rise was less marked in the absence of Ca2+ and could be antagonized by 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate-hydrochloride (TMB-8), an inhibitor of calcium release from internal stores. 5-HT induced a shape change reaction in the presence or absence of extracellular Ca2+, but the pEC50 of 5-HT was slightly higher in the presence of the cation. Shape change reaction and [Ca2+]i-rise showed similar time courses. Various 5-HT-agonists caused a rise of [Ca2+]i, whereas 5-HT-antagonists, but not the 5-HT-uptake inhibitor desmethylimipramine and the alpha 2-adrenoceptor antagonist yohimbine, counteracted the 5-HT-induced rise of the cation in a stereospecific manner. The antagonists were more potent than the agonists. The orders of potencies of the drugs affecting [Ca2+]i and platelet shape were similar. It is concluded that stimulation of 5-HT2-receptors of platelets causes a rapid release of intracellular calcium which, by activation of the contractile system, mediates the shape change reaction.