GLUTAMATE-RECEPTOR AGONISTS MODULATE [CA2+](I) IN ISOLATED RAT MELANOTROPES

Although glutamate is the predominant excitatory amino acid in the ver tebrate central nervous system (CNS) where it affects a variety of phy siological processes and pathophysiological states, the role that glut amate receptors may play Neurohypophysis outside the CNS has not been clearly established. In the present study, the Intermediate lobe effec ts of N-methyl-D-aspartate (NMDA), no-2,3-dihydro-5-methyl-3-oxo-4-iso xazolepropanoic acid (AMPA) kainate, and metabotropic glutamate recept or agonists and antagonists were investigated on neuroendocrine melano tropes of the rat pars intermedia using single-cell dual-wavelength mi crofluorometry and the Ca(2+)sensitive probe, fura-2, to monitor chang es in [Ca2+](i). Glutamate induced a rapid, concentration-dependent ri se in [Ca2+](i) with an EC(50) Of 24 mu M that was Mg2+-sensitive and dependent on the presence of extracellular Ca2+. NMDA increased [Ca2+] (i) in a glycine-dependent manner with an EC(50) of 83 mu M that was b locked by 1 mu M MK-801 and 1 mM Mg2+. The non-NMDA receptor agonists kainate, AMPA, and quisqualate increased [Ca2+](i) with an EC(50) Of 1 24, 5 and 8 mu M, respectively. Responses to kainic acid were blocked by 10 mu M CNQX and were shown to be sensitive to Mg2+ and dihydropyri dine. AMPA stimulation was the most potent, and glutamate stimulation was the most efficacious at mediating increases in [Ca2+](i). The meta botropic receptor-specific agonist, trans-ACPD, failed to induce a cha nge in [Ca2+](i). The glutamate-induced Ca2+ influx was about half of that elicited by a 50 mM K+-induced membrane depolarization and activa tion of voltage-sensitive Ca2+ channels. These results demonstrate the presence of glutamate receptors on rat melanotropes and suggest that glutamate receptors in the intermediate lobe of the pituitary may prov ide the excitatory counterbalance to the well-described secretoinhibit ing input via dopamine and gamma-aminobutyric acid receptors.