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Transduction of the modulatory effect of catecholamines at the mammalian motor neuron terminal
H Chen1, W F Dryden, Y N Singh
1Department of Pharmacology, University of Alberta, Edmonton, Canada.
Abstract:
MEPP frequency (f) was measured in mouse phrenic nerve hemidiaphragm preparations during exposure to adrenoceptor agonist and antagonist drugs. Epinephrine, norepinephrine (NE), and phenylephrine caused a concentration-dependent increase in frequency that was blocked by prazosin but not by yohimbine or nadolol. Isoproterenol had no effect on MEPP(f). The response to NE was not affected by prior incubation of the tissues with pertussis toxin. The response was, however, reduced or abolished by prior exposure to drugs, the actions of which include protein kinase inhibition, and also to a calmodulin inhibitory concentration of W-7. H-7, an inhibitor of protein kinase C and of cyclic nucleotide-dependent kinases, was ineffective. The response to NE was enhanced by 10 mM Li+. The data indicate the existence of a presynaptic alpha 1-adrenoceptor in the motor neuron terminal and suggest that modulation of transmitter release might be mediated by inositol triphosphate liberation, Ca2+ release into the cytosol and activation of a calmodulin-dependent system.
Insights
This study identified a presynaptic alpha 1-adrenoceptor in mouse motor neurons. This receptor modulates neurotransmitter release via calcium and calmodulin signaling pathways.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Presynaptic adrenoceptors play a role in regulating neurotransmitter release.
- The specific subtypes and signaling pathways involved in motor neuron modulation are not fully elucidated.
Purpose of the Study:
- To investigate the role of adrenoceptors in modulating neurotransmitter release at the mouse phrenic nerve terminal.
- To identify the specific adrenoceptor subtype and downstream signaling mechanisms involved.
Main Methods:
- Measurement of miniature end-plate potential (MEPP) frequency in mouse phrenic nerve hemidiaphragm preparations.
- Exposure to various adrenoceptor agonists and antagonists.
- Assessment of the effects of protein kinase and calmodulin inhibitors, pertussis toxin, and lithium.
Main Results:
- Epinephrine, norepinephrine, and phenylephrine increased MEPP frequency in a concentration-dependent manner.
- This effect was blocked by prazosin (an alpha 1-adrenoceptor antagonist) but not by yohimbine or nadolol.
- Isoproterenol had no effect.
- The response was inhibited by protein kinase inhibitors and W-7 (calmodulin inhibitor), but not by H-7.
- Lithium enhanced the response to norepinephrine.
Conclusions:
- Data indicate the presence of a presynaptic alpha 1-adrenoceptor in the motor neuron terminal.
- Modulation of transmitter release likely involves inositol triphosphate liberation, intracellular calcium release, and calmodulin activation.