tropisetron and pyridoxal-phosphate-6-azophenyl-2--4--disulfonic-acid

GABAergic and glycinergic inhibitory synaptic transmissions in substantia gelatinosa (SG; lamina II of Rexed) neurons of the spinal dorsal horn play an important role in regulating nociceptive transmission from the periphery. It has not yet been well known whether each of the inhibitory transmissions plays a distinct role in the regulation. We report an involvement of neurotransmitters in GABAergic but not glycinergic transmission enhancement produced by the PLA(2) activator melittin, where the whole-cell patch-clamp technique is applied to the SG neurons of adult rat spinal cord slices. Glycinergic but not GABAergic spontaneous inhibitory postsynaptic current (sIPSC) was increased in frequency and amplitude by melittin in the presence of nicotinic, muscarinic acetylcholine, and α(1)-adrenergic receptor antagonists (mecamylamine, atropine, and WB-4101, respectively). GABAergic transmission enhancement produced by melittin was unaffected by the 5-hydroxytryptamine 3 receptor and P2X receptor antagonists (ICS-205,930 and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, respectively). Nicotinic and muscarinic acetylcholine receptor agonists [(-)-nicotine and carbamoylcholine, respectively] and norepinephrine, as well as melittin, increased GABAergic sIPSC frequency and amplitude. A repeated application of (-)-nicotine, carbamoylcholine, and norepinephrine, but not melittin, at an interval of 30 min produced a similar transmission enhancement. These results indicate that melittin produces the release of acetylcholine and norepinephrine, which activate (nicotinic and muscarinic) acetylcholine and α(1)-adrenergic receptors, respectively, resulting in GABAergic but not glycinergic transmission enhancement in SG neurons. The desensitization of a system leading to the acetylcholine and norepinephrine release is slow in recovery. This distinction in modulation between GABAergic and glycinergic transmissions may play a role in regulating nociceptive transmission.

Topics: Acetylcholine; Adrenergic alpha-Antagonists; Animals; Atropine; Carbachol; Dioxanes; gamma-Aminobutyric Acid; Glycine; Indoles; Inhibitory Postsynaptic Potentials; Male; Mecamylamine; Melitten; Muscarinic Antagonists; Neurons; Nicotine; Nicotinic Antagonists; Norepinephrine; Purinergic P2X Receptor Antagonists; Pyridoxal Phosphate; Rats; Serotonin Antagonists; Substantia Gelatinosa; Synaptic Transmission; Tropisetron

Cardiovascular responses to intravenous administration of a piperamide analogue, LASSBio 365, were investigated in anesthetized rats. LASSBio 365 [62.5-1000 microg/kg, intravenously (IV)] has potent cardiovascular effects that include hypotension and bradycardia, accompanied by a brief pressor effect and apnea. Bilateral vagotomy or atropine injection (2 mg/kg, IV) completely abolished the bradycardia. A drop in blood pressure was abolished in bivagotomized rats. However, it was only inhibited in atropine-treated rats. The apnea was inhibited by both treatments. The Bezold-Jarisch reflex (ie, hypotension, bradycardia, and apnea) induced by LASSBio 365 is altered neither by 5-HT3 antagonist (tropisetron, 0.1 mg/kg, intraarterially) nor by the P2x antagonist (PPADS, 8.6 mg/kg, IV). The pressor component was affected neither by any of these interventions nor by the 5-HT2 antagonist (ritanserin, 0.5 mg/kg, i.a.). In capsaicin-pretreated rats (50 mg/kg, subcutaneously), all responses evoked by LASSBio 365 were abolished, including the pressor effect, which was inhibited. The data show that LASSBio 365 evokes the Bezold-Jarish reflex, neither via serotonergic receptors nor purinergic receptors but perhaps via the vanilloid pathway.

Topics: Animals; Apnea; Atropine; Benzodioxoles; Blood Pressure; Bradycardia; Capsaicin; Heart Rate; Hypotension; Indoles; Injections, Intravenous; Male; Morpholines; Pyridoxal Phosphate; Rats; Rats, Sprague-Dawley; Reflex; Ritanserin; Tropisetron; Vagotomy