The pharmacology of the piperidine dicarboxylates on the crustacean neuromuscular junction.
The effects of the four cis-piperidine dicarboxylate analogues (PDAs) on the neuromuscular junction of the hermit crab (Eupagurus bernhardus) were examined. Intracellular recordings of evoked excitatory junction potentials (EJPs) and the membrane potential were made. All four analogues were active as agonists and depolarized the fibre membrane. The dose-response curves for the 2,3 and 2,6-piperidine dicarboxylates were similar to that for L-glutamate but were one tenth as potent. The dose-response curves for the 2,4 and 2,5-piperidine dicarboxylates had shallower gradients and lower maxima indicating lower potencies. The piperidine dicarboxylates non-competitively antagonized and glutamate-induced potential and reversibly attenuated the amplitude of the junction potential, with no change in membrane input resistance. The decrease in amplitude of the glutamate-induced potentials produced by a train of ionophoretic pulses was reversibly blocked by incubation with any of the dicarboxylates. The results indicate that the piperidine dicarboxylates prevent the development of receptor desensitization. The significance of these findings is discussed.
D000818:Animals; D033381:Anomura; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009469:Neuromuscular Junction / Q000502:physiology*; D010875:Pipecolic Acids / Q000494:pharmacology*
D005971:Glutamates; D010875:Pipecolic Acids; D018698:Glutamic Acid; C029262:2,3-piperidinedicarboxylic acid; C041089:2,6-piperidinedicarboxylic acid; C041090:2,5-piperidinedicarboxylic acid; C041091:2,4-piperidinedicarboxylic acid