Differential effects of omega-conotoxin GVIA, nimodipine, calmidazolium and KN-62 injected intrathecally on the antinociception induced by beta-endorphin, morphine and [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin administered intracerebroventricularly in the mouse.
We previously reported that beta-endorphin and morphine administered supraspinally produce antinociception by activating different descending pain-inhibitory systems. To determine the role of spinal calcium channels, calmodulin and calcium/calmodulin-dependent protein kinase II in the production of antinociception induced by morphine, [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO) or beta-endorphin administered supraspinally, the effects of nimodipine (an L-type calcium channel blocker), omega-conotoxin GVIA (an N-type voltage-dependent calcium channel blocker), calmidazolium (a calmodulin antagonist) or KN-62 (a calcium/calmodulin-dependent protein kinase II inhibitor) injected intrathecally (i.t.) on the antinociception induced by morphine, DAMGO or beta-endorphin administered intracerebroventricularly (i.c.v.) were examined in the present study. Antinociception was assessed by the mouse tail-flick test. The i.t. injection of nimodipine (from 0.024 to 2.4 pmol), omega-conotoxin GVIA (from 0.0033 to 0.33 pmol), calmidazolium (from 0.0015 to 0.15 pmol) or KN-62 (from 0.0014 to 0.14 pmol) alone did not affect the basal tail-flick latencies. The i.t. pretreatment of mice with nimodipine, omega-conotoxin GVIA, calmidazolium or KN-62 dose dependently attenuated the inhibition of the tail-flick response induced by beta-endorphin administered i.c.v. However, the inhibition of the tail-flick response induced by morphine or DAMGO administered i.c.v. was not changed by i.t. pretreatment with nimodipine, omega-conotoxin GVIA, calmidazolium or KN-62. The results suggest that spinally located L- and N-type calcium channels, calmodulin and calcium/calmodulin-dependent protein kinase II may be involved in the modulation of antinociception induced by beta-endorphin, but not morphine and DAMGO, administered supraspinally.
Suh
H W
HW
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chunchon, Kangwon-Do, South Korea. hwsuh@sun.hallym.ac.kr
Song
D K
DK
Choi
S R
SR
Huh
S O
SO
Kim
Y H
YH
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009553:Nimodipine / Q000008:administration & dosage / Q000494:pharmacology*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D013116:Spinal Cord / Q000201:enzymology; D001615:beta-Endorphin / Q000008:administration & dosage / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D004745:Enkephalins; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010455:Peptides; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C031938:calmidazolium; D009553:Nimodipine; D001615:beta-Endorphin; C063302:KN 62; D009020:Morphine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D020866:omega-Conotoxin GVIA; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases