Nicotine-induced alteration in Tyr-Gly-Gly and Met-enkephalin in discrete brain nuclei reflects altered enkephalin neuron activity.
Nicotine acts in CNS, but the pathways and mechanisms of its actions are poorly understood. Recent studies suggest an interaction between brain nicotinic receptors and endogenous opioid peptides. Acute administration of nicotine may alter enkephalin release without affecting brain enkephalin level. Tyr-Gly-Gly has been shown previously to be an extraneuronal metabolite of opioid peptides derived from proenkephalin A. Concentrations of Tyr-Gly-Gly in brain were used to provide an index of enkephalin release in vivo. Thus we examined the thesis that nicotine alters brain neuronal enkephalin release, by measuring Tyr-Gly-Gly levels in specific brain nuclei from rats treated with nicotine 0.3 mg/kg SC 10 min before decapitation. Of 30 brain regions investigated, acute nicotine increased Tyr-Gly-Gly immunoreactivity in nucleus accumbens and in lower brain stem areas including dorsal raphe, pontine reticular formation, gigantocellular reticular formation, locus coeruleus, sensory trigeminal nucleus and the caudal part of ventrolateral medulla oblongata. Concomitantly, nicotine produced a significant decrease in native Met-enkephalin in central amygdala, flocculo-nodular lobe of cerebellum, caudal part of the ventrolateral medulla and intermediolateral cell column of the spinal cord. It is probable that the effects of nicotine to increase Tyr-Gly-Gly and alter Met-enkephalin concentration are mediated by nicotine-induced release of enkephalin at these brain sites. Furthermore, some of the physiologic and pharmacologic effects of nicotine may be mediated by such enkephalin release.
Houdi
A A
AA
Department of Medicine, University of Kentucky, Lexington 40546-0236.
Pierzchala
K
K
Marson
L
L
Palkovits
M
M
Van Loon
G R
GR
D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D004744:Enkephalin, Methionine / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D009842:Oligopeptides / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D009479:Neuropeptides; D009842:Oligopeptides; C044757:tyrosyl-glycyl-glycine; D004744:Enkephalin, Methionine; D009538:Nicotine