Long-term opiate exposure leads to increase in synapsin I in rat spinal cord-dorsal root ganglion cocultures.
Cocultures of spinal cord and dorsal root ganglion cells contain relatively high concentrations of kappa-opiate receptors. We have previously shown that acute kappa-opiate agonist treatment reduces phosphorylation of synapsin I stimulated by depolarizing agents (such as 60 mM KCl). Here we show that prolonged opiate treatment increases the levels of synapsin I immunoreactivity in the cells. Several opiate agonists, such as U50488, ethylketocyclazocine, dynorphin, and [D-Ala2,D-Leu5]enkephalin, caused a 3.0-3.4-fold increase in the immunoreactive level of synapsin I. The effect of the kappa-agonist U50488 on the up-regulation of synapsin I was dose dependent and was blocked by the kappa-opiate antagonist norbinaltor-phimine. The results suggest that continued activation of opiate receptors by chronic agonist treatment up-regulates the levels of synapsin I. This increase in synapsin I could contribute to the development of tolerance to opiates.
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Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
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Vogel
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D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003584:Cytological Techniques; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D009294:Narcotics / Q000494:pharmacology*; D010766:Phosphorylation; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism*
D000700:Analgesics; D009294:Narcotics; D011759:Pyrrolidines; D016704:Synapsins; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer