Transduction of the modulatory effect of catecholamines at the mammalian motor neuron terminal.
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.
Chen
H
H
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Dryden
W F
WF
Singh
Y N
YN
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology; D002395:Catecholamines / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009045:Motor Endplate / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects*; D009411:Nerve Endings / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology
D002147:Calmodulin; D002395:Catecholamines; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011942:Receptors, Adrenergic, alpha; D013449:Sulfonamides; D010656:Phenylephrine; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019204:GTP-Binding Proteins; D009638:Norepinephrine; D004837:Epinephrine