Vasopressin and amastatin induce V-1-receptor-mediated suppression of excitatory transmission in the rat parabrachial nucleus

We examined actions of arginine vasopressin (AVP) and amastatin (an inhibit or of the aminopeptidase that cleaves AVP) on synaptic currents in slices o f rat parabrachial nucleus using the nystatin-perforated patch recording te chnique. AVP reversibly decreased the amplitude of the evoked, glutamate-me diated, excitatory postsynaptic current (EPSC) with an increase in paired-p ulse ratio. No apparent changes in postsynaptic membrane properties were re vealed by ramp protocols, and the inward current induced by a brief applica tion of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid was unchan ged 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 (M anning compound, 10 mu M). Bath application of an aminopeptidase inhibitor, amastatin(10 mu M), reduced the evoked EPSC, and AVP induced further synap tic depression in the presence of amastatin. Amastatin's effects also could be antagonized by the Manning compound. Corticotropin-releasing hormone sl ightly 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 synap tic action. The results suggest that AVP has suppressant effects on glutama tergic transmission by acting at V-1 AVP receptors, possibly through a pres ynaptic mechanism involving a pertussis-toxin- and cholera-toxin-resistant pathway.