Simultaneous effects of the platelet 5-HT2 and alpha 2-adrenergic receptor populations on phosphoinositide hydrolysis

The interaction of multiple receptor populations on a common second messenger system is a critical aspect of cell function and may be involved in pathology. We studied the interactions of the 5-HT2, alpha 2-adrenergic and prostaglandin (PGI2) receptors on phosphoinositide (PI) turnover in human platelets. Serotonin and epinephrine (EPI) stimulated PI hydrolysis in a dose-dependent manner. The PI turnover response to serotonin was mediated by the 5-HT2 receptor. The PI response to EPI was mediated by alpha 2-adrenergic receptors. An additive PI turnover response was generated by the combination of 5-HT and EPI. The sum of the maximal responses to 5-HT (72.5 +/- 4.9%) and EPI (56.0 +/- 4.2%) approximated the maximal response (129.3 +/- 9.5) to the combination. Prostacyclin (PGI2) at 1 microgram/mL reduced PI turnover by 21.8 +/- 1.1%. The PI response to 5-HT and EPI was not significantly altered once the reduction in the baseline PI turnover by PGI2 is taken into account. Similarly, PGI2 did not reduce PI hydrolysis stimulated by a combination of 5-HT (0.2 mM) and EPI (0.1 mM) once the decrease in baseline was taken into account (p greater than 0.20). The summation of serotonin stimulation of PI turnover by a combination of both epinephrine and serotonin was blocked by either yohimbine or ketanserin. These studies indicate: (1) the pool of phospholipases appears to exceed the maximal capacity of the individual alpha 2-adrenergic and 5-HT2 receptor populations to activate this second messenger system. (2) inhibition of serotonin or epinephrine-stimulated PI turnover by prostacyclin is due to a lowering of basal PI turnover. Future studies should examine other cell systems to assess the generalizability of these findings regarding the differences in effects on a second messenger system when activated by one receptor population as opposed to two different receptor types.