Nalorphine: actions at an opiate receptor on frog skeletal muscle fibers.

Intracellular microelectrode studies were conducted to investigate the actions of the partial agonist-antagonist nalorphine at an opiate receptor on functional frog skeletal muscle fiber membranes. In high bath concentrations (greater than or equal to 10(-4) M), nalorphine alone produces agonist actions similar to the "full" opiate agonists. These actions were (i) to depress both the sodium and potassium (gNa and gK) conductance increases due to electrical stimulation by a nonspecific local anestheticlike mechanism and (ii) to depress gNa by a specific opiate receptor mediated mechanism. In a much lower bath concentration (1 X 10(-8) M) nalorphine acts to antagonize the specific opiate receptor mediated depression of gNa produced by the "full" agonist meperidine. Thus in this preparation nalorphine, "the partial antagonist," has the same actions as naloxone, which is often considered to be a full antagonist. The quantitative differences observed in the effects of these two opiate antagonists are discussed.

Stereospecificity of an opiate action on the excitable membrane of frog skeletal muscle fibres.

Intracellular microelectrode studies were conducted to examine the actions of the optical isomers levorphanol and dextrorphan on the isolated frog sartorius muscle preparation. Both isomers, in bath concentrations which had minimal effect on action potential amplitude and gNa (3 X 10(-5) M), caused a large depression of gK. High bath concentrations (3 X 10(-4) M) of both drugs caused an initial depression of sodium and potassium conductance processes, gNa and gK, respectively, however only levorphanol, but not dextrorphan, could produce a specific, late-occurring depression of gNa that could be blocked by the opiate antagonists, nalorphine or naloxone. These findings indicate that the late-occurring depressant effect on gNa is stereospecific and reinforce previous findings which demonstrated that opiate drugs interact with opiate receptors associated with the sodium channels of the frog muscle fibre membranes.

Phencyclidine-induced release of [3H]dopamine from chopped striatal tissue.

Phencyclidine was examined for its ability to release [3H]dopamine ([3H]DA) from prelabelled chopped rat striatal tissue. A dynamic perfusion system was used in order to minimize the effects of drugs on uptake mechanisms. Cocaine and S-(+)-amphetamine were used to distinguish uptake inhibition from a neurotransmitter releasing action. Phencyclidine, starting at 3 microM caused a dose-dependent increase in efflux of [3H]DA from chopped striatal tissue. In this same preparation, cocaine, a known neuronal uptake inhibitor of dopamine, was unable to release [3H]DA except in the largest dose of 100 microM. S-(+)Amphetamine, a known releaser of neuronal dopamine, was found to be about ten times more potent then phencyclidine in causing a dose-dependent release of [3H]DA. The results of the above experiments are discussed in relation to the ability of phencyclidine to decrease the synaptosomal accumulation of [3H]DA. It is concluded that some of the psychoactive effects of phencyclidine may be due to the ability of phencyclidine to elicit a release of dopamine from dopaminergic neurons.

Basis of phencyclidine's ability to decrease the synaptosomal accumulation of 3H-catecholamines.

Mixed cortical and hypothalamic synaptosomes and striatal synaptosomes were allowed to accumulate 3H-norepinephrine and 3H-dopamine, respectively, for 5 min in the absence and presence of phencyclidine. The results indicate that phencyclidine probably decreased the accumulation of 3H-norepinephrine into mixed cortical and hypothalamic synaptosomes by only blocking the uptake of the 3H-amine. On the other hand, part of the decrease in accumulation of 3H-dopamine elicited by 10 muM of PCP was probably caused by PCP releasing previously accumulated 3H-dopamine.