Antinociceptive mechanisms of dipsacus saponin C administered intrathecally in mice.
Dipsacus saponin C (DSC) administered intrathecally (i.t.) showed antinociceptive effect in a dose-dependent (from 3.75 to 30 microg) manner as measured by the tail-flick assay. The antinociception induced by DSC at the dose of 30 microg reached at peak 7.5 min and almost returned to the control level after 60 min. 5-Amino-valeric acid (5-AVA, a GABA(A) receptor antagonist, from 1 to 20 microg) and SR 95531 (a GABA(B) receptor antagonist, from 0.1 to 2 ng) dose-dependently attenuated i.t. administered DSC-induced increase of the inhibition of the tail-flick response. The i.t. injection of yohimbine (an alpha(2)-adrenergic receptor antagonist, from 1 to 20 microg) and methysergide (a serotonin receptor antagonist, from 1 to 20 microg), but not naloxone (from 2 to 8 microg), significantly attenuated inhibition of the tail-flick response induced by DSC (30 microg) administered i.t. Sulfated cholecystokinin (CCK, from 0.05 to 0.5 ng) injected i.t. significantly reduced the inhibition of the tail-flick response induced by DSC (30 microg) administered i.t. Our results suggest that DSC shows an antinociceptive effect when it is administered spinally and GABA(A), GABA(B), alpha(2)-adrenergic and serotonin receptors located at the spinal cord level, but not opioid receptors, may be involved in DSC-induced antinociception. Furthermore, CCK may play an important role for the modulation of i. t. injected DSC-induced antinociception.
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Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 1 Okchun-Dong, Chunchon, 200-702, Korea. hesuh@sun.hallym.ac.kr
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D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002681:China; D004305:Dose-Response Relationship, Drug; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009828:Oleanolic Acid / Q000031:analogs & derivatives*; D010147:Pain Measurement / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism; D018079:Receptors, GABA / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2; D011949:Receptors, Cholecystokinin; D018079:Receptors, GABA; D011985:Receptors, Serotonin; D012503:Saponins; D012702:Serotonin Antagonists; C085394:dipsacus saponin C; D009828:Oleanolic Acid