Chlorpromazine, but not chlorpromazine sulphoxide, stimulates transmitter release from motor nerve terminals
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
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.
|Number of pages||5|
|Publication status||Published - 29 Dec 1987|
- Animals, Neurotransmitter Agents, Neuromuscular Junction, Calcium, Motor Endplate, Membrane Potentials, Chlorpromazine, Calmodulin, Magnesium, Structure-Activity Relationship, Rana temporaria, Motor Neurons