Implication of the descending dynorphinergic neuron projecting to the spinal cord in the (+)-matrine- and (+)-allomatrine-induced antinociceptive effects.
We previously reported that either (+)-matrine (matridin-15-one) or (+)-allomatrine (the C-6 epimer of matrine)-induced antinociceptive effect was attenuated by s.c. pretreatment with a kappa-opioid receptor (KOR) antagonist nor-binaltorphimine (nor-BNI), indicating the critical role of KORs in antinociceptive effects induced by these alkaloids. In the present study, we found that i.c.v. administration of either (+)-matrine- or (+)-allomatrine induced antinociceptive effects in the mouse tail-flick and warm-plate test, whereas these alkaloids when given spinally failed to induce antinociception. In the guanosine-5'-O-(3-[(35)S]thio)trisphosphate ([(35)S]GTPgammaS) binding assay, we demonstrated that neither (+)-matrine nor (+)-allomatrine produced the stimulation of [(35)S]GTPgammaS binding in the membranes of the spinal cord, indicating that (+)-matrine- and (+)-allomatrine-induced supraspinal antinociceptive actions was not due to a direct stimulation of KORs by these alkaloids. Therefore, we next investigated the involvement of dynorphin A (1-17) release at the spinal or supraspinal site in (+)-matrine- or (+)-allomatrine-induced antinociception. The i.c.v. pretreatment with an antiserum against dynorphin A (1-17) could not affect the antinociceptive effect induced by s.c. treatment of (+)-matrine. In contrast, the s.c.-administered (+)-matrine- and (+)-allomatrine-induced antinociceptive effect was significantly attenuated by i.t. pretreatment of an antiserum against dynorphin A (1-17). The present data suggest that either (+)-matrine or (+)-allomatrine when given i.c.v. may stimulate the descending dynorphinergic neuron, resulting in the stimulation of KORs in the spinal cord, and this phenomenon in turn produces the antinociception in mice.
Higashiyama
Kimio
K
Institute of Medicinal Chemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, Japan. kimio@hoshi.ac.jp
Takeuchi
Yosuke
Y
Yamauchi
Takayasu
T
Imai
Satoshi
S
Kamei
Junzo
J
Yajima
Yoshinori
Y
Narita
Minoru
M
Suzuki
Tsutomu
T
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000700:Analgesics / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D004399:Dynorphins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009292:Narcotic Antagonists / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D011807:Quinolizines; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D000093842:Matrines
D000470:Alkaloids; D000700:Analgesics; D009292:Narcotic Antagonists; D010936:Plant Extracts; D011807:Quinolizines; D004399:Dynorphins; D000093842:Matrines