strychnine and homocysteic-acid

A high density of nitric oxide synthesising enzyme is present in sympathetic preganglionic neurones in the spinal cord. It has been shown that nitric oxide is released as a consequence of synaptic activity. In the present study in anaesthetised rats we determined if nitric oxide acted as a retrograde messenger molecule to modulate the excitatory effects on the renal sympathetic spinal network elicited by paraventricular nucleus stimulation. Neurones in the latter nucleus were stimulated by microinjecting DLH and drugs were applied to the spinal cord via an intrathecal catheter with the tip positioned at T9-T10. Intrathecal application of the nitric oxide donors, sodium nitroprusside or [3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine] significantly increased tonic activity in the renal sympathetic nerve. In contrast synaptic activity evoked by intrathecal glutamate or by paraventricular nucleus stimulation was enhanced by preventing nitric oxide generation with intrathecal N(G)-monomethyl-L-arginine monoacetate (L-NMMA) a nitric oxide synthase inhibitor. Enhancement of synaptically induced renal nerve activity was also observed following intrathecal glycine receptor inhibitor strychnine. Strychnine was without effect when it was given after L-NMMA. It was concluded that paraventricular nucleus excitation of renal sympathetic neurones is subject to inhibitory modulation by released nitric oxide and it is suggested the latter acts via glycine interneurones.

Topics: Action Potentials; Animals; Arginine; Blood Pressure; Bronchodilator Agents; Drug Interactions; Enzyme Inhibitors; Glutamic Acid; Glycine; Glycine Agents; Homocysteine; Hydrazines; Injections, Spinal; Kidney; Male; Neurons; Nitric Oxide; Nitric Oxide Donors; Nitroprusside; omega-N-Methylarginine; Paraventricular Hypothalamic Nucleus; Rats; Rats, Wistar; Spinal Cord; Strychnine; Sympathetic Nervous System; Synapses

1. We have examined the effects of iontophoretic application of antagonists to excitatory amino acid (EAA) receptors, as well as glycine and gamma-aminobutyric acid (GABA), on rhythmically active (RA) brain stem neurons during cortically induced masticatory activity (RMA) in the anesthetized guinea pig. Ten of these neurons were antidromically activated at latencies of 0.3-0.9 ms by stimulation of the trigeminal motor nucleus (MoV). 2. RA neurons were divided into closer and opener type according to the phase of activation during RMA. Iontophoretic application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a specific non-N-methyl-D-aspartate (NMDA) receptor antagonist, suppressed discharge of both closer and opener type RA neurons during RMA. In contrast, iontophoretic application of 3-((1)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a specific NMDA receptor antagonist, was not effective in suppressing discharge of most opener type RA neurons but did reduce activity of closer type RA neurons. 3. Spike discharge of most RA neurons was time locked to each cortical stimulus during RMA. Some of the RA neurons were activated at a short latency to short pulse train stimulation of the cortex in the absence of RMA. In most cases CNQX reduced such time-locked responses during RMA and greatly reduced discharge evoked by short pulse stimulation of the cortex in all cases. In contrast, CPP was not as effective in suppressing either the time-locked responses during RMA or the discharge evoked by short pulse train stimulation of the cortex. 4. D,L-Homocysteic acid (HCA) application produced low level maintained discharge in RA neurons before RMA induction. When RMA was evoked in combination with HCA, rhythmical burst discharges with distinct interburst periods during the opening phase of RMA were observed in most closer type RA neurons. In contrast, during RMA in combination with HCA application, opener type RA neurons showed burst discharges that were modulated during the RMA cycle but lacked distinct interburst periods during the closer phase of the cycle. 5. During application of strychnine (STR), a glycine antagonist, discharge of closer type RA neurons increased in the opener phase of RMA during continuous HCA application. In contrast, bicuculline methiodide (BIC), a GABA antagonist, did not increase unit discharge of closer type RA neurons in the opener phase of RMA. 6. It is concluded that closer type RA neurons receive, alternatively, EAA-mediated

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Brain Mapping; Brain Stem; Cerebral Cortex; Electric Stimulation; Excitatory Amino Acid Antagonists; GABA Antagonists; Guinea Pigs; Homocysteine; Interneurons; Mastication; Membrane Potentials; Neural Inhibition; Neural Pathways; Piperazines; Reaction Time; Receptors, Glycine; Receptors, N-Methyl-D-Aspartate; Strychnine; Synaptic Transmission; Trigeminal Nerve; Trigeminal Nuclei

In the spinal cord of the pentobarbitone-anaesthetised cat, microelectrophoretic RU 5135, a steroid derivative, was a potent strychnine-like glycine antagonist, having less effect on the inhibition by GABA of neuronal firing.

Topics: Action Potentials; Androstanes; Animals; Azasteroids; Bicuculline; Cats; GABA Antagonists; Glycine; Homocysteine; Interneurons; Steroids, Heterocyclic; Strychnine