Neuropeptides
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The effect of nicotine injected intrathecally (i.t.) on the inhibition of the tail-flick response induced by morphine, beta-endorphin, D-Pen2,5-enkephalin (DPDPE), or [(trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeocetamide)] (U50,488H) administered i.t. was studied in ICR mice. The i.t. injection of nicotine alone at doses from 1 to 12 microg produced only a minimal inhibition of the tail-flick response. Morphine (0.2 microg), beta-endorphin (0.1 microg), DPDPE (0.5 microg) or U50,488H (6 microg) caused only slight inhibition of the tail-flick response. ⋯ However, i.t. injected nicotine at the same doses was not effective in enhancing the inhibition of the tail-flick response induced by beta-endorphin, DPDPE, or U50,488H administered i.t. Our results suggest that stimulating nicotinic receptors located in the spinal cord may enhance the antinociception induced by morphine administered spinally. However, the activation of nicotinic receptors at the spinal level may not be involved in modulating the antinociception induced by beta-endorphin, DPDPE, and U50,488H administered spinally.
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The modulation by morphine of the spinal release of met-enkephalin-like material (MELM) was investigated in anaesthetized rats whose intrathecal space was perfused with an artificial CSF (ACSF). Morphine (10 microM in the ACSF), as well as a mu- (DAGO, 10 microM) or delta opioid receptor agonist (DTLET, 10 microM), significantly decreased the outflow of MELM. The effects of morphine and DTLET were prevented by the delta antagonist, naltrindole (10 microM), but not by naloxone (10 microM). ⋯ In contrast to the inhibition induced by morphine (with or without naloxone) which was preventable by 10 microM naltrindole, the inhibition of MELM release by morphine plus norbinaltorphimine was only partly reduced by naltrindole. Thus, concomitant stimulation of mu, delta and kappa 1 receptors might account for the apparent delta opioid receptor-dependent inhibition of MELM release by morphine. Indeed, its potential inhibitory effect through the stimulation of mu receptors (normally prevented by the concomitant stimulation of kappa 1 receptors) becomes efficient only when kappa 1 receptors are blocked.
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Dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), a naturally occurring peptide isolated from arboreal frog skin, is endowed with outstanding structural and biological features. It has no structural community with the sequence of mammalian opioid peptides and is a unique example of a D-aminoacid containing peptide which is synthesized via ribosomal route. Dermorphin is the most potent of the opioid peptides or opiates in producing long lasting analgesia and catalepsy. ⋯ Identification was achieved by chromatographic comparison with synthetic standards and immunological analysis. A peptide behaving like authentic dermorphin was detected (2 ng/g) in rat small intestine. Immunoreactive species of higher Mr were also detected in the brain, adrenal glands and gastrointestinal tract, they may represent extended forms of dermorphin or homologous peptides.