Modulation of intracellular calcium changes and glutamate release by neuropeptide Y1 and Y2 receptors in the rat hippocampus: differential effects inCA1, CA3 and dentate gyrus

In the present work, we investigated the role of pre- and post-synaptic neu ropeptide Y1 (NPY1) and Y2 receptors on the calcium responses and on glutam ate release in the rat hippocampus. In cultured hippocampal neurones, we ob served that only NPY1 receptors are involved, in the modulation of intracel lular free calcium concentration ([Ca2+](i)). In 88% of the neurones analys ed, the increase in the [Ca2+](i), in response to depolarization with 50 mm KCl, was inhibited by 1 muM [Leu31,Pro34]NPY, whereas 300 nM NPY13-36 was without effect. However, studies with hippocampal synaptosomes showed that both NPY1 and Y2 receptors can modulate the [Ca2+](i) and glutamate release . The pharmacological characterization of the NPY-induced inhibition of glu tamate release indicated that Y2 receptors play a predominant role, both in the modulation of Ca2+-dependent and -independent glutamate release, Howev er, we could distinguish between Y1 and Y2 receptors by using [Leu31,Pro34] NPY and NPY13-36. Active pre-synaptic Y1 receptors are present in the denta te gyrus (DG) as well as in the CA3 subregion, but its activity was not rev ealed by using the endogenous agonist, NPY. Concerning the Y2 receptors, th ey are present in the three subregions (CA1, CA3 and DG) and were activated by either NPY13-36 or NPY. The present data support a predominant role for NPY2 receptors in mediating NPY-induced inhibition of glutamate release in the hippocampus, but the physiological relevance of the presently describe d DG and CA3 presynaptic NPY1 receptors remains to be clarified.