Ptychodiscus brevis toxin-induced depression of spinal reflexes involves 5-HT via 5-HT3 receptors modulated by NMDA receptor.
The involvement of 5-hydroxytryptaminergic (5-HT) system for the Ptychodiscus brevis toxin (PbTx)-induced depression of spinal reflexes was evaluated. The reflex potentials were recorded at ventral root by stimulating the corresponding dorsal root in neonatal rat spinal cord in vitro. Superfusion of PbTx (2.8-84microM) depressed the monosynaptic (MSR) and polysynaptic (PSR) reflexes in a concentration-dependent manner. The depression of the reflexes was maximal with 84microM of the toxin. Ondansetron (0.1microM), a 5-HT(3) receptor antagonist, blocked the PbTx-induced depression of MSR and PSR. Spiperone (a 5-HT(2A) antagonist) or ketanserin (5-HT(2A/2C) antagonist and also at 5-HT(1B/1D)) failed to block the PbTx-induced depression of the reflexes. The 5-HT concentration of the cords was increased by four-fold after exposure to PbTx (28microM) and the increase was not seen in the cords pretreated with dl-2 amino-5-phosphonovaleric acid (APV, a NMDA receptor antagonist). Superfusion of 5-HT or phenylbiguanide (PBG, a 5-HT(3) receptor agonist) also produced depression of the spinal reflexes in a concentration-dependent manner. The 5-HT-induced depression of reflexes was blocked by ondansetron but not by spiperone. The results demonstrate that the PbTx-induced depression of spinal reflexes involves 5-hydroxytryptamine via 5-HT(3) receptors modulated by NMDA receptor.
Singh
Jitendra N
JN
Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
Gupta
Rajesh
R
Deshpande
Shripad B
SB
D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D003864:Depression, Chemical; D004141:Dinoflagellida / Q000737:chemistry*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008387:Marine Toxins / Q000633:toxicity*; D009498:Neurotoxins / Q000633:toxicity*; D017294:Ondansetron / Q000494:pharmacology; D035964:Oxocins; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000502:physiology*; D012018:Reflex / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013126:Spinal Nerve Roots / Q000502:physiology; D013134:Spiperone / Q000494:pharmacology
D001645:Biguanides; D018492:Dopamine Antagonists; D008387:Marine Toxins; D009498:Neurotoxins; D035964:Oxocins; C051732:Ptychodiscus brevis T2 toxin; D016194:Receptors, N-Methyl-D-Aspartate; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D012701:Serotonin; D017294:Ondansetron; D013134:Spiperone; D007650:Ketanserin; C008846:phenyl biguanide