ACCUMULATION OF ENKEPHALIN, PROENKEPHALIN MESSENGER-RNA, AND NEUROPEPTIDE-Y IN IMMUNOLOGICALLY DENERVATED RAT ADRENAL-GLANDS - EVIDENCE FORDIVERGENT PEPTIDE REGULATION

To investigate transsynaptic effects on peptides of adrenal chromaffin cells in the rat, presynaptic sympathetic terminals were destroyed by intravenous injection of monoclonal antibodies to acetylcholinesteras e. At several times thereafter, neuropeptide Y (NPY)-like immunoreacti vity (NPY-IR) and methionine-enkephalin-like immunoreactivity (Met-Enk -IR) were measured by radioimmunoassay. Within 2 days of antibody inje ction, adrenal Met-Enk-IR increased five- to 10-fold and NPY-IR increa sed 50%. These effects were accompanied by large increases in proenkep halin A mRNA assayed by polymerase chain reaction. The peptide respons es could reflect either an acute activation, as presynaptic terminals degenerated, or a chronic synaptic inactivation after terminal degener ation. To test the possibilities, muscarinic and nicotinic receptors w ere inhibited by repeated injection of atropine (1 mg/kg) and chloriso ndamine (5 mg/kg). Measurements of urinary free catecholamine excretio n showed that this treatment prevented the paroxysmal release of norep inephrine and reduced the release of epinephrine that normally followe d injection of acetylcholinesterase antibodies. When the drugs were gi ven alone for 2 or 4 days, adrenal Met-Enk-IR increased modestly and N PY-IR remained steady or declined. When given together with acetylchol inesterase antibodies, the cholinergic antagonists blocked the increas e of NPY-IR but not Met-Enk-IR. Adding naloxone (1 mg/kg) to the treat ment regimen enhanced the blockade of epinephrine excretion and largel y prevented the antibody-induced increase in Met-Enk-IR. These finding s indicate that adrenal NPY and enkephalin are not regulated identical ly. Adrenal NPY behaves as though controlled by transsynaptic choliner gic input. On the other hand, adrenal enkephalin may be regulated by a dditional or different mechanisms, possibly involving peptidergic tran smission or synaptic inactivation.