Kynurenic acid as an additional endogenous anti-aggregatory factor

Kynurenic acid [KNA] is an endogenous metabolite of tryptophan that has been characterized both in the brain and various peripheral organs that included blood vessels, kidneys, hearts, intestine and the eye. Its release from the vascular tissues which also release prostacyclin and nitric oxide directed us to investigate its influence on platelets aggregation. Exposure of guinea-pig platelets to KNA in concentrations ranging from 0.1 to 2mM inhibited adenosine diphosphate [ADP] and arachidonic acid [AA] induced aggregations in a dose-dependent manner.The inhibitory dose 50 values against ADP and AA were found to be 1.1 +/- 0.06 and 0.9 +/- 0.08 mM respectively. [N=8]. The anti-aggregatory effect was significantly reversed in presence of exogenous Ca[2+]. Elevation of the level of the plasma by 0.5mM Ca[2+] reversed the anti-aggregatory effect KNA by 60 +/- 4.5 and 71.5 +/- 6.3% against ADP and AA, respectively [P<0.01, N=8]. It is suggested that KNA may be considered as an additional endogenous anti-aggregatory factor

Recent advances in the roles of calcium ions [Ca2+] and their antagonism in various body functions

This review deals mainly with the importance and the various roles played by Ca[2+] ions [Ca[2+]] in mammalian body functions and the various implications following the prevention of release from. the intracellular stores or the influx from the extracellular fluids. It discusses the molecular mechanisms through which Ca[2+] mediate muscular contractility, secretion of hormones, release of autacoids, neurotransmitters, cytokines and bone formation. Furthermore, the reveiw points out the various disturbances and diseases that follow inappropriate and excessive Ca[2+] release in various organs and the available pharmacological means to normalise it. The review also deals with the various means that regulate the intracellular and the extracellular levels of Ca[2+]. Special emphasis was given to the various types of Ca[2+] channels so far discovered in the mammalian organs. The review concluded by pointing out the shortcomings of the existing organic Ca[2+] channel blockers and the importance of discovery of organ and channel selective Ca[2+] channel blockers with the ultimate goal of decreasing the multiple side effects observed following the use of the existing Ca[2+] channel blockers