Nicotine-induced alterations in brain regional concentrations of native and cryptic Met- and Leu-enkephalin.
The distribution of cryptic forms (larger enkephalin-containing peptides) in neostriatum, hypothalamus, spinal cord T3-L1 and neurointermediate lobe of pituitary were determined by radioimmunoassay. Optimal conditions for enzymic hydrolysis of the cryptic enkephalins by trypsin and carboxypeptidase B were established. The proportion of total Met- and Leu-enkephalin represented by native pentapeptide varied markedly among these central nervous system regions. Also, the distributions of native and cryptic Met-enkephalin were distinct from that of Leu-enkephalin. Chromatographic separation by HPLC of immunoreactive Met-enkephalin peptides revealed only two peaks corresponding to Met-enkephalin and Met-enkephalin sulfoxide in rather equal amounts. Hydrolysis of cryptic Met-enkephalin also produced only two HPLC-separable peaks of immunoreactive Met-enkephalin, again corresponding to Met-enkephalin and Met-enkephalin sulfoxide. Bioactivity of cryptic striatal Met-enkephalin after hydrolysis was demonstrated by antinociception and catalepsy in rats following its intracerebroventricular injection. Repeated short-term administration of nicotine, 0.1 mg/kg IP six times at 30 min intervals, produced significant increases in native and cryptic Met-enkephalin in striatum, consistent with an increase in neuronal release of Met-enkephalin together with increases in synthesis and processing of proenkephalin A in this brain region. This regimen of nicotine also decreased levels of native Met-enkephalin and of both native and cryptic Leu-enkephalin in neurointermediate lobe, consistent with nicotine-induced release of both proenkephalin A- and prodynorphin-derived peptides from neurointermediate lobe.
VA Medical Center, Lexington, KY 40511.
K
K
Pierzchala
A A
AA
Houdi
G R
GR
Van Loon
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003342:Corpus Striatum / Q000032:analysis; D004743:Enkephalin, Leucine / Q000032:analysis* / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000032:analysis* / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D006868:Hydrolysis; D007031:Hypothalamus / Q000032:analysis; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D010902:Pituitary Gland / Q000032:analysis; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004745:Enkephalins; D011498:Protein Precursors; C029992:proenkephalin; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D009538:Nicotine