The differential effect of morphine and beta-endorphin administered intracerebroventricularly on pERK and pCaMK-II expression induced by various nociceptive stimuli in mice brains.
The present study was performed to characterize the differential molecular mechanisms of morphine and beta-endorphin which are injected intracerebroventiricularly in mice. In the immunoblot assay, the increases of phosphorylated extracellular signal-regulated protein kinase (pERK) as well as phosphorylated calcium/calmodulin-dependent protein kinase IIalpha (pCaMK-IIalpha) expression induced by noxious stimuli were attenuated by intracerebroventricular (i.c.v.) beta-endorphin pretreatment in the hypothalamus, but not by i.c.v. morphine pretreatment. In addition to these immunoblot results, immunohistochemical study also showed that the attenuation of pERK or pCaMK-IIalpha immunoreactivity elicited by i.c.v. pretreatment of beta-endorphin mainly occurred in the paraventricular nucleus of the hypothalamus (PVN). We also investigated the effect of morphine and beta-endorphin on pERK and pCaMK-IIalpha expression in the locus coeruleus (LC). I.c.v. injection of morphine significantly increased pERK as well as pCaMK-IIalpha expression in the locus coeruleus, while beta-endorphin increased only pCaMK-IIalpha in the LC. In addition, beta-endorphin significantly attenuated pERK expression induced by SP i.t. injection. These results suggest that the antinociceptive effects of supraspinally administered morphine and beta-endorphin are involved with differentially intracellular signal transduction molecules-pERK, pCaMK-IIalpha in the PVN and the LC.
Seo
Young-Jun
YJ
Department of Pharmacology and Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon, Gangwon-Do, South Korea.
Kwon
Min-Soo
MS
Choi
Hee-Woo
HW
Jang
Jeong-Eun
JE
Lee
Jin-Koo
JK
Jung
Jun-Sub
JS
Park
Soo-Hyun
SH
Suh
Hong-Won
HW
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000096:biosynthesis*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis*; D005557:Formaldehyde; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology; D013373:Substance P; D001615:beta-Endorphin / Q000008:administration & dosage / Q000494:pharmacology*
D000701:Analgesics, Opioid; D005557:Formaldehyde; D013373:Substance P; D001615:beta-Endorphin; D009020:Morphine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases