title: Protein kinase C activity alters the effect of μ-opioid receptors on inhibitory postsynaptic current in the striosomes.
abstract: We have previously reported that earlier blockade of protein kinase C (PKC) augments the suppressive effect of μ-opioid receptors (MORs) on the GABAergic inhibitory postsynaptic current (IPSC) in the MOR-rich striosomes of the striatum. Interestingly, striatal medium-spiny neurons have muscarinic acetylcholine receptor subtypes M1 and M4, among which M1 activates the phosphoinositide signaling pathway yielding PKC. In this study, we examined whether acetylcholine regulates the effects of MOR on presynaptic IPSC by binding to the M1 receptor, and found that IPSC suppression by the MOR agonist, [D-Ala-N-Me-Phe, Gly-ol]-enkephalin, was significantly augmented and prolonged by the PKC inhibitor chelerythrine and attenuated by the PKC activator, phorbol 12, 13-dibutyrate. This modulatory action by chelerythrine was mimicked by the muscarinic antagonist atropine and the M1-specific antagonist pirenzepine, whereas M2-M4 antagonists had no discernible effect. These results suggest that PKC activity modulates the effect of MOR by muscarinic receptors in the striosomes.
authors.affiliation: Neuropathophysiology Research Group, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Inoue
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Aosaki
authors.forename: Masami
authors.initials: M
authors.lastname: Miura
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D011976:Receptors, Muscarinic; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D011493:Protein Kinase C; D000109:Acetylcholine