Second messenger pathways in the modulation of neurotransmitter release.
Activation of receptors on postganglionic sympathetic nerve endings can alter the amount of noradrenaline release during a train of nerve impulses. These changes may be produced by the enzyme-linked synthesis of second messenger molecules within the nerve terminal. Cyclic AMP analogues enhance noradrenaline release and two hormones adrenaline and ACTH appear to enhance noradrenaline release through activation of adenylate cyclase. Activation of the phospholipase C/protein kinase C pathway also elevates stimulation-induced noradrenaline release and angiotensin enhancement of noradrenaline release appears to act through this pathway. On the other hand, receptors which inhibit noradrenaline release (alpha 2-adrenoceptors, muscarinic M2 receptors and neuropeptide Y receptors) do not act through either of these signal transduction pathways. Since these inhibitory systems are neurotransmitter activated and relay information on a nerve pulse to nerve pulse time scale back to the nerve ending a fast activation and deactivation rate of modulation is required. This may be better served by direct modulation of ion channels without a slow intervening enzyme step. Activation of protein kinase C by phorbol esters produces relatively large increases (two-threefold) in stimulation-induced noradrenaline release and this enzyme may also have a physiological role. Protein kinase C may be an appropriate target for drugs to manipulate transmitter release and development of selective activators and inhibitors of the many protein kinase C isoenzymes may prove clinically useful in diseases with inappropriate transmitter release profiles.
Majewski
H K
HK
Prince Henry's Institute of Medical Research, Melbourne, Vic.
Musgrave
I F
IF
D000262:Adenylyl Cyclases / Q000502:physiology; D000320:Adrenergic Fibers / Q000502:physiology; D000818:Animals; D001338:Autonomic Fibers, Postganglionic / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D018377:Neurotransmitter Agents; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D009638:Norepinephrine