Batrachotoxin is present in remarkably high amounts in the skin of Phyllobates terribilis. Levels of batrachotoxin tend to be reduced when P. terribilis is maintained in captivity, but even after being confined for up to 6 years, these frogs were still at least five times more toxic than other Phyllobates species used by natives for poisoning blowgun darts. Batrachotoxin was not detectable in F1 progeny reared to maturity in captivity. Nerve and muscle preparations from wild-caught frogs and from the nontoxic F1 frogs were both insensitive to batrachotoxin. The regulatory site controlling sodium-channel activation and permeability appears to have been minimally altered to prevent interaction with batrachotoxin, but is still sensitive to other sodium conductance activators (veratridine, grayanotoxin) to which the frogs arenot exposed naturally.

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authors have requested readers to note that a p-D-glutamyl residue rather than the p-LIglutamyl residue, implied in the text, was used for the calculations. The conclusions drawn in the paper are correct, since the D and L configurations of the p-glutamyl residue adopt almost identical conformations in thyrotropin releasing factor (TRF). It is possible to use the results in Tables 2-4 of the original paper to obtain the lowenergy conformations of TRF by simply reversing the sign of {,. The conformations thus obtained will not be the exact energy minima, but will represent all of the low-energy conformations closely. In order to illustrate this point, the calculations of Table 2 in the original text (for "p-D-glutamyl" TRF) were repeated using a p-L-glutamyl residue, and the minimum-energy results are given below ( Table 1). The dihedral angles for all conformations are essentially the same except that the sign of {l is reversed. It should be noted that the N8 conformer of structure D is now only 0.1 kcal/mol higher in energy than conformer NE of structure A. The similarity of the "p-D-glutamyl" and "p-L-glutamyl" TRF conformations suggests that the former should be active as a thyrotropin releasing factor.

Phencyclidine [PCP; (1-phencyclohexyl)piperidine] is a general anesthetic and hallucinogen that has prolonged duration of action and is also psychotomimetic (1, 2). It potentiates the direct and indirect evoked muscle twitch, an effect that seems to be related to a marked blockade of potassium conductance (3). In addition, after an initial twitch potentiation the neuromuscular transmission is blocked as a result of a direct effect of PCP on the ionic channel of the acetylcholine (AcCho) receptor. PCP decreases the peak amplitude of the end-plate current (epc) in a voltage-and time-dependent manner, causes significant nonlinearity of the current-voltage relationship and marked acceleration of the decay time of both epc and miniature end-plate current (mepc), and concomitantly shortens the mean channel lifetime without alteration of the single channel conductance (4,5 MATERIALS AND METHODS Electrophysiological Techniques. Experiments were performed at room temperature (20-22°C) on sciatic nerve sartorius muscle preparations of the frog Rana pipiens, except that extrajunctional AcCho sensitivity measurements were made on 10-to 15-day denervated rat soleus muscles. The Ringer solutions used, nerve stimulation, intracellular recordings of the resting membrane potential, action potential, end-plate potential (epp), and miniature end-plate potential (mepp), delayed rectification, and microiontophoresis of AcCho were as described (6, 10, 11). The voltage-clamp circuitry and recording and analysis of the epc fluctuations in response to iontophoretic application of AcCho were similar to those described previously and were analyzed by an on-line PDP-11 computer. The drugs were superfused from micropipets by pressure with close application to the end-plate region.Biochemical Techniques. Membrane preparation from the electric organ of T. ocellata was as described (8). [piperidyl-3,4-3H(N)

The action of phencyclidine [1-(1-phenylcyclohexyl)piperidine; PCP] and its behaviorally active analog (mamino-PCP) and oftwo behaviorally inactive analogs [m-nitro-PCP and I-piperidinocyclohexanecarbonitrile (PCC)] were examined in this study. In a test of spatial alternation performance in rats, PCP and m-amino-PCP were much more potent behavior modifiers than were PCC and m-nitro-PCP. We studied the effects of the drugs on the ionic channels of the electrically excitable membrane and of the nicotinic acetylcholine (AcCho) receptors at the neuromuscular junction of frog skeletal muscle. All four compounds blocked the indirectly elicited muscle twitch and depressed the amplitude and rate of rise of directly elicited muscle action potentials. They also caused a voltage-and concentration-dependent decrease in the peak amplitude of the endplate current but did not react with the nicotinic AcCho receptor. These observations indicate that the four compounds have comparable blocking effects on the ionic channels associated with the nicotinic AcCho receptor. In contrast, the behaviorally active agents could be distinguished from behaviorally inactive ones by their effects on K+ conductance. PCP and m-amino-PCP blocked delayed rectification in frog sartorius muscles, prolonged the muscle action potential more than 2-fold, and markedly potentiated the directly elicited muscle twitch. The behaviorally active compounds also blocked depolarization-induced 8Rb4 efflux from rat brain synaptosomes (presumably a measure of K+ conductance) and increased quantal content at the frog neuromuscular junction. In these actions, m-nitro-PCP was much less effective, and PCC was relatively ineffective. Because PCP and m-amino-PCP are much more potent behavior modifiers than PCC and m-nitro-PCP, we suggest that the behavioral effects ofPCP and m-amino-PCP, may be due to a block of K+ conductance and enhancement of transmitter release at central neurons.Phencyclidine [1-(l-phenylcyclohexyl)piperidine; PCP], a drug that produces agitation, depression, and convulsions in humans, also has strong abuse liability. When taken chronically or in large doses, it has profound effects on mental status in man; these effects range from euphoria to psychotic disturbance and often may be difficult to distinguish from schizophrenia (1). In many animals, PCP is considered the anesthetic ofchoice; however, induction of anesthesia is associated with agitation, tremors, and involuntary movement (1).The behavioral effects ofPCP have been attributed to its wide spectrum of action on synaptic transmission in the central nervous system (1). We have reported that PCP is a potent inhibitor of K+ conductance of electrically excitable membranes; it also blocks the ionic channel associated with the nicotinic acetylcholine (AcCho) receptor (2, 3). The key question is whether or not the behavioral effects can be attributed to either of these actions ofPCP. In an effort to settle this question, we compared the actions of two behaviorally inactive analogs of ...