tGLP-1 action on the isolated hypothalamo-neurohypophysial system under glutamate receptor blockade.

The isolated rat hypothalamo-neurohypophysial system was used to investigate possible mechanisms of glucagon-like peptide-1 (7-36) amide (tGLP-1) effects on the vasopressin/oxytocin (AVP/OXY) release. The non-selective inhibition of synaptic transmission as brought about by excess of MgSO(4) in the incubation medium completely abolished the tGLP-1-induced AVP release and attenuated OXY secretion. The non-specific blockade of excitatory amino acid receptors with kynurenic acid (KA) completely suppressed the tGLP-1-induced AVP but not OXY release. Specific inhibition of NMDA receptors suppressed the tGLP-1-evoked AVP release without affecting tGLP-1-induced OXY secretion. Selective blockade of non-NMDA receptors did not affect either tGLP-1-induced AVP or OXY release. It is concluded that tGLP-1 can influence the function of AVP neurons indirectly, most probably via the glutamatergic system through NMDA receptors. On the other hand, tGLP-1-evoked activation of OXY neurons, at least in part, seems to be a result of direct tGLP-1 activation of these neurons.