A subtype of opioid kappa-receptor is coupled to inhibition of Gi1-mediated phospholipase C activity in the guinea pig cerebellum.
PLC activity was stimulated either by 1-100 microM of GTP or by 100-3,000 microM Ca2+ in lysed synaptosomal membranes of the guinea pig cerebellum. The kappa-opioid receptor agonist selectively inhibited the PLC activity stimulated by 100 microM GTP, but not by 100-3,000 microM Ca2+. Pretreatment of membranes with PTX abolished such a kappa-agonist-induced inhibition of PLC activity. The reconstitution of Gi1, but not of Go purified from porcine brains with PTX-treated membranes showed a complete recovery of the kappa-agonist-inhibition of PLC activity. These findings suggest that a novel subtype kappa-receptor mediates inhibition of PLC through inhibiting the intrinsic activity of PTX-substrate G-proteins.
Misawa
H
H
Tokyo Metropolitan Institute for Neuroscience, Japan.
Ueda
H
H
Katada
T
T
Ui
M
M
Satoh
M
M
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000201:enzymology*; D019204:GTP-Binding Proteins / Q000302:isolation & purification / Q000502:physiology*; D006150:Guanine Nucleotides; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006168:Guinea Pigs; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D006150:Guanine Nucleotides; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D010566:Virulence Factors, Bordetella; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium