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Interactions between adenosine and phorbol esters or lithium at the frog neuromuscular junction
1Laboratory of Pharmacology, Gulbenkian Institute of Science, Oeiras, Portugal.
British Journal of Pharmacology
|May 1, 1990
Summary
Adenosine inhibits neuromuscular transmission, but protein kinase C activation reverses this effect. The phosphoinositide pathway, not adenylate cyclase, mediates adenosine
Area of Science:
- Neuroscience
- Cellular Signaling
- Pharmacology
Background:
- Adenosine and its analogs inhibit neuromuscular transmission.
- Signal transduction pathways, including phosphoinositides/protein kinase C and adenylate cyclase, are crucial in cellular regulation.
- Understanding these pathways is key to elucidating neurotransmission modulation.
Purpose of the Study:
- To investigate the interaction between adenosine's effects and signal transduction systems on neuromuscular transmission.
- To determine the role of phosphoinositides/protein kinase C and adenylate cyclase pathways in adenosine-mediated inhibition.
- To explore potential therapeutic targets for modulating neuromuscular function.
Main Methods:
- Experiments were conducted on the innervated sartorius muscle of frogs, with twitches blocked by high magnesium concentrations.
- Investigated the effects of protein kinase C activator (PDAc) and inhibitor (polymyxin B, H-7).
- Examined the impact of lithium chloride (phosphoinositide pathway modulator) and forskolin (adenylate cyclase activator).
Main Results:
- Protein kinase C activator (PDAc) increased endplate potential (e.p.p.) amplitude and quantal content, and attenuated adenosine's inhibitory effects.
- Protein kinase C inhibitor (polymyxin B) decreased e.p.p. amplitude and quantal content, but did not affect adenosine's inhibition.
- Lithium chloride increased e.p.p. amplitude and quantal content, with this effect attenuated by adenosine.
- Forskolin (adenylate cyclase activator) increased e.p.p. amplitude and quantal content.
Conclusions:
- The phosphoinositides/protein kinase C transducing system appears to be involved in adenosine's inhibitory effect on neuromuscular transmission.
- The adenylate cyclase transducing system does not seem to mediate adenosine's inhibitory action.
- Findings suggest that modulating the protein kinase C pathway could influence neuromuscular transmission.