Accumulation of enkephalin, proenkephalin mRNA, and neuropeptide Y in immunologically denervated rat adrenal glands: evidence for divergent 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 acetylcholinesterase. At several times thereafter, neuropeptide Y (NPY)-like immunoreactivity (NPY-IR) and methionine-enkephalin-like immunoreactivity (Met-Enk-IR) were measured by radioimmunoassay. Within 2 days of antibody injection, adrenal Met-Enk-IR increased five- to 10-fold and NPY-IR increased 50%. These effects were accompanied by large increases in proenkephalin A mRNA assayed by polymerase chain reaction. The peptide responses could reflect either an acute activation, as presynaptic terminals degenerated, or a chronic synaptic inactivation after terminal degeneration. To test the possibilities, muscarinic and nicotinic receptors were inhibited by repeated injection of atropine (1 mg/kg) and chlorisondamine (5 mg/kg). Measurements of urinary free catecholamine excretion showed that this treatment prevented the paroxysmal release of norepinephrine and reduced the release of epinephrine that normally followed injection of acetylcholinesterase antibodies. When the drugs were given alone for 2 or 4 days, adrenal Met-Enk-IR increased modestly and NPY-IR remained steady or declined. When given together with acetylcholinesterase antibodies, the cholinergic antagonists blocked the increase of NPY-IR but not Met-Enk-IR. Adding naloxone (1 mg/kg) to the treatment regimen enhanced the blockade of epinephrine excretion and largely prevented the antibody-induced increase in Met-EnK-IR. These findings indicate that adrenal NPY and enkephalin are not regulated identically. Adrenal NPY behaves as though controlled by transsynaptic cholinergic input. On the other hand, adrenal enkephalin may be regulated by additional or different mechanisms, possibly involving peptidergic transmission or synaptic inactivation.
Brimijoin
S
S
Department of Pharmacology, Mayo Clinic, Rochester, Minnesota 55905.
Dagerlind
A
A
Rao
R
R
McKinzie
S
S
Hammond
P
P
D000110:Acetylcholinesterase / Q000276:immunology; D000311:Adrenal Glands / Q000294:innervation* / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001483:Base Sequence; D002714:Chlorisondamine / Q000494:pharmacology; D018680:Cholinergic Antagonists; D017931:DNA Primers / Q000737:chemistry; D004745:Enkephalins / Q000235:genetics* / Q000378:metabolism*; D004837:Epinephrine / Q000652:urine; D008297:Male; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000378:metabolism*; D009638:Norepinephrine / Q000652:urine; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D018680:Cholinergic Antagonists; D017931:DNA Primers; D004745:Enkephalins; D009478:Neuropeptide Y; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D001285:Atropine; D000110:Acetylcholinesterase; D002714:Chlorisondamine; D009638:Norepinephrine; D004837:Epinephrine