Glutamic acid (GA) and norepinephrine (NE) stimulate luteinizing hormone-releasing hormone (LHRH) release via release of nitric oxide (NO) from NOergic neurons in the arcuate-median eminence region. To determine if GA releases LHRH via direct stimulation of NOergic neurons, or via stimulation of noradrenergic terminals, arcuate median eminence explants from male rats were incubated with various compounds, and the LHRH release into the medium was measured. GA-induced release of LHRH was completely blocked by phentolamine (1 mu M), an alpha receptor blocker, which, by itself, had no effect on the release. Nitroprusside (NP), which spontaneously releases NO, more than doubled LHRH release. To determine if alpha receptors on the LHRH neuron are required for the action of NP, the tissue was incubated with phentolamine, plus NP. Phentolamine had no effect on the LHRH-releasing action of NP. The results are interpreted to mean that GA activates the release of NE from the noradrenergic terminals. This acts on alpha receptors on the NOergic neuron to produce the release of NO. This NO diffuses to the LHRH terminals and induces release of LHRH.