EFFECT OF CATECHOLAMINE DEPLETION AND DENERVATION ON NEUROPEPTIDE-Y (NPY) AND TYROSINE-HYDROXYLASE (TH) MESSENGER-RNA LEVELS IN RAT SYMPATHETIC-GANGLIA

Neuropeptide Y (NPT) and noradrenaline (NA) are synthesized and stored in sympathetic nerves and concomitantly released in response to appro priate stimuli. The two substances have been reported to interact on v arious levels: postjunctionally, by mutually potentiating their vasoco nstrictor effects, prejunctionally, by inhibiting each other's release . The possibility of an interaction on the levels of their synthesis w as investigated in this study. Specific cDNA probes were used for the measurement of the steady state levels of the mRNAs encoding prepro-NP Y and tyrosine hydroxylase (TH) in the superior sympathetic cervical a nd stellate ganglia of rats. Reserpine (5 mg/kg) was administered for inducing catecholamine depletion. This caused a large decrease in the NA content of the heart associated with an about 50% reduction in card iac NPY levels. Ganglionic NPY and TH mRNA levels increased 3-6 fold a s compared to vehicle treated animals. To determine whether this effec t was due to transynaptic induction, superior cervical ganglia were de centralized in a subgroup of rats. Decentralized ganglia displayed sig nificantly lower NPY and TH mRNA levels than intact ones. The response to reserpine was almost completely prevented by decentralization. The se Observations indicate that the activation of gene expression of NPY and TH by reserpine depends on intact ganglionic innervation and is t herefore reflexly mediated. Trans-synaptic induction may regulate NPY and TH mRNA levels also under basal conditions.