Abstract
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.
Original language | English |
---|---|
Pages (from-to) | 397-401 |
Number of pages | 5 |
Journal | Brain Research |
Volume | 437 |
Issue number | 2 |
Publication status | Published - 29 Dec 1987 |
Keywords
- Animals
- Neurotransmitter Agents
- Neuromuscular Junction
- Calcium
- Motor Endplate
- Membrane Potentials
- Chlorpromazine
- Calmodulin
- Magnesium
- Structure-Activity Relationship
- Rana temporaria
- Motor Neurons