Potentiation of Enkephalin Action by Peptidase Inhibitors in Rat Locus Ceruleus in Vitro1

Intracellular recordings were made from locus ceruleus (LC) neurons in slices of rat pens. It has been shown previously that opioids inhibit firing and hyperpolanze LC neurons by activating mu-opioid receptors. Concentration-response curves were con-structed by measuring the hyperpolarization, or outward current at-60 mV, caused by various opioid agonists added to the superfusing solution. Peptidase inhibitors (kelatorphan, bestatin and thiorphan) each increased the potency of Met-enkephalin, Leu-enkephalin and metorphamide but had no effect of their own on the LC neurons. Kelatorphan (20 M) produced a 7-fold shift to the left of the Met-enkephalin dose-response curve. Higher concentrations produced no further shift. Thiorphan (3 tM) and bestatin (20 M) each had a smaller potentiating effect on the Met-enkephalin hyperpolarization. The effects of Tyr-o-Ala-GIy-MePhe-Gly-ol and noradrenaline were not potentiated by thes