Investigating GABA and its function in platelets as compared to neurons.
We have recently suggested that platelets could be used as a model for neuronal receptors. In this paper we have investigated gamma-aminobutyric acid (GABA) metabolism and GABA receptors in platelets and in cultured neurons to see whether platelets' GABA mimics neuronal GABA receptor activities. We used the ELISA technique for detecting the GABA concentration in platelet rich plasma and cultured neurons. The functional effects of GABA and its receptor ligands on platelets were determined using an aggregometer. We found that the GABA concentration is 30% lower in platelets than in neurons and in both preparations GABA was metabolized by GABA transaminase (GABA-T). GABA potentiated calcium dependent platelet aggregation with a higher value in washed platelets suspension (WPS) then in platelet rich plasma (PRP). This effect was inhibited by benzodiazepines, calcium channel blockers and the selective phosphoinositide 3-kinase antagonist Wortmannin. GABA neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. We concluded that platelets could be further developed to be used as a peripheral model to study neuronal GABAergic function and its abnormality in diseases such as epilepsy and schizophrenia. Furthermore our results indicated that PI3-kinase is involved in calcium dependent GABA induced platelet aggregation as this synergistic effect is inhibited by Wortmannin in dose dependent manner.
Kaneez
Fatima Shad
FS
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270. ftmshad@gmail.com
Saeed
Sheikh Arshad
SA
D000818:Animals; D001792:Blood Platelets / Q000737:chemistry / Q000502:physiology*; D002118:Calcium; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D009474:Neurons / Q000737:chemistry / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases; D010974:Platelet Aggregation; D018079:Receptors, GABA / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism* / Q000502:physiology
D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D019869:Phosphatidylinositol 3-Kinases; D002118:Calcium