THE USE OF THE HUMAN NEUROBLASTOMA SH-SY5Y TO STUDY THE EFFECT OF 2ND-MESSENGERS ON NORADRENALINE RELEASE

1. Recent data suggesting that the human neuroblastoma SH-SY5Y is a su itable cell line in which to study the effect of second messengers on NA release are discussed in the context of current views on exocytosis . 2. Release of NA is evoked by depolarization, as well as activation of muscarinic (M(3)) and bradykinin (B-2) receptors in SH-SY5Y cells w hich have not been differentiated by the addition of growth factors. 3 . Evoked release is enhanced by activation of protein kinase C. 4. Act ivation of protein kinase C decreases the changes in intracellular cal cium evoked by carbachol, bradykinin and 100 mM K+. 5. SH-SY5Y express N-type and L-type voltage sensitive Ca2+-channels. L-Type Ca2+-channe ls are coupled to NA release under conditions of weak depolarization. However with strong depolarization (100 mM K+) both L-type and N-type channels are involved. 6. Muscarinic- and neuropeptide Y receptors are coupled to the inhibition of Ca2+ channel activity.