Vasopressin and amastatin induce V1-receptor-mediated suppression of excitatory transmission in the rat parabrachial nucleus

We examined actions of arginine vasopressin (AVP) and amastatin (an inhibitor of the aminopeptidase that cleaves AVP) on synaptic currents in slices of rat parabrachial nucleus using the nystatin-perforated patch recording technique. AVP reversibly decreased the amplitude of the evoked, glutamate-mediated, excitatory postsynaptic current (EPSC) with an increase in paired-pulse ratio. No apparent changes in postsynaptic membrane properties were revealed by ramp protocols, and the inward current induced by a brief application of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid was unchanged after AVP. The reduction induced by 1 mu M AVP could be blocked by a V-1 AVP receptor antagonist, [d(CH2)(5)(1)-O-Me-Tyr(2)-Arg(8)]-vasopressin (Manning compound, 10 mu M). Bath application of an aminopeptidase inhibitor, amastatin(10 mu M), reduced the evoked EPSC, and AVP induced further synaptic depression in the presence of amastatin. Amastatin's effects also could be antagonized by the Manning compound. Corticotropin-releasing hormone slightly increased the EPSC at 1 mu M, and coapplication with AVP attenuated the AVP response. Pretreatment of slices with 1 mu g/ml cholera toxin or 0.5 mu g/ml pertussis toxin for 20 h did not significantly affect AVP's synaptic action. The results suggest that AVP has suppressant effects on glutamatergic transmission by acting at V-1 AVP receptors, possibly through a presynaptic mechanism involving a pertussis-toxin- and cholera-toxin-resistant pathway.