Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of three irreversible anticholinesterase agents, echothiophate (217MI), tertiary methylamine analog of 217MI (217AO) and Tetram, on end plate currents (e.p.c.s) of Rana pipiens cutaneous pectoris muscle were studied using electrophysiological techniques. All three compounds (217MI, 1-10 microM; 217AO, 1-25 microM; and Tetram, 1-50 microM) decreased the rate of e.p.c. decay (alpha) to the same extent as neostigmine (10 microM), a reversible anticholinesterase agent. Decay remained a single exponential at all membrane potentials. 217MI and its derivatives greatly reduced the normal voltage dependence of alpha represented by the slope (H = mV-1) of log alpha vs. membrane potential, in contrast to neostigmine which had no effect on H. Suppression of Ach release by the addition of 4 mM Mg++ to end-plates did not alter the reduction of H by 217AO indicating that the anticholinesterase-induced decrease in H is not simply due to an increased interaction between Ach and its receptors. Additionally, the pretreatment of end-plates with methanesulfonyl fluoride, also an irreversible cholinesterase agent, did not modify the effects of 217AO and Tetram on H. 217MI and its derivatives, at low concentrations which altered H, did not affect [3H]PCP or [125I]alpha-bungarotoxin binding to Torpedo californica Ach receptor-rich membranes. It is concluded that these agents alter H by an effect on the Ach receptor ion channel complex unrelated to either esterase inhibition or channel block.
 ...
PMID:Echothiophate and cogeners decrease the voltage dependence of end-plate current decay in frog skeletal muscle. 248 Oct 33

Ion entry into neurons occurs either through receptor-operated channels (ROC) or voltage-operated channels (VOC). The function of ROC depends crucially on the action of agonists, antagonists or compounds modulating particular types of receptors (GABA A, NMDA, Ach N receptors). The function of VOC is closely connected with the activity of protein kinases and the processes of phosphorylation of membrane proteins (K+, Na+, Ca2+ channels). Gamma aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the vertebrate brain. The GABA A receptor is a oligomeric complex of multiple binding sites and chloride channel. This complex contains recognition sites for GABA, anxiolytics such as benzodiazepine, anxiogenic--beta-carboline, and convulsant such as picrotoxin. Chloride ion channel plays a crucial role in anxiogenic, anxiolytic and convulsant activities. Glutamic acid is the main endogenous neurotransmitter for N-methyl-D-aspartate (NMDA)-type excitatory amino acid receptor. NMDA receptors connected with Ca2+ channel, have multiple modulatory sites which are affected by a wide range of compounds. There are NMDA and competitive NMDA antagonists site, the glycine site, the phencyclidine (PCP) site and the binding site of Mg2+ ions in this receptor complex. Calcium entry through NMDA receptors may be important in the etiology of many psychiatric disorders. VOC mediate rapid, voltage-gated changes in ion permeability during action potentials in neurons. Electrophysiological studies indicate the existence of three types of VOC (K+, Na+, Ca2+ channels). In number of neurons various subtypes of Ca2+ channels (P, T, N and L-type) occur together. Among them, the L-type calcium channel has been first described and most thoroughly studied. The L-type calcium channel is localized on nerve terminals in the pre and postsynaptic parts, as well as on cell bodies and may be involved in the mechanism of action of psychotropic drugs. Chronic treatment with various psychotropic drugs changes the density of voltage-dependent Ca2+ channels in the central nervous system. Thus calcium entry through both VOC and ROC may be important in the etiology of many psychiatric disorders.
 ...
PMID:Receptor and voltage-operated ion channels in the central nervous system. 871 58