Chlorpromazine, but not chlorpromazine sulphoxide, stimulates transmitter release from motor nerve terminals.
Treatment of frog neuromuscular preparations with chlorpromazine (5 mumol/l) resulted in a marked rise in miniature endplate potential (MEPP) frequency of greater than 100% within 30 min, and an increase in evoked transmitter release (quantal content 5-15) of about 35%. Treatment with chlorpromazine sulphoxide (5 microM), a derivative of chlorpromazine with a much lower affinity for calmodulin, had very little effect on either form of transmitter release. It is concluded that stimulatory effects of calmodulin-binding drugs at the nerve terminal may well be exerted through calmodulin inhibition. The stimulatory effect of chlorpromazine on MEPP frequency was markedly reduced in preparations bathed in EGTA-containing Ca2+-free saline, but the response was largely restored by raising the temperature by 3-4 degrees C. It is argued that despite this partial dependence on [Ca2+]o, stimulation of transmitter secretion by chlorpromazine is likely to be mediated by inhibition of calmodulin-activated Ca2+-ATPases, and consequent elevation of [Ca2+]i.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000502:physiology; D002746:Chlorpromazine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects* / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000502:physiology*; D011896:Rana temporaria; D013329:Structure-Activity Relationship
D002147:Calmodulin; D018377:Neurotransmitter Agents; C026714:opromazine; D008274:Magnesium; D002118:Calcium; D002746:Chlorpromazine