Presynaptic 5-HT3 receptors evoke an excitatory response in dorsal vagal preganglionic neurones in anaesthetized rats.
1. Recordings were made from a total of sixty-four vagal preganglionic neurones in the dorsal vagal motor nucleus (DVMN) of pentobarbitone sodium anaesthetized rats. The effects of ionophoretic administration of Mg2+ and Cd2+, inhibitors of neurotransmitter release, and the selective NMDA and non-NMDA receptor antagonists (+/-)-2-amino-5-phosphono-pentanoic acid (AP5) and 6,7-dinitroquinoxaline-2,3-dione (DNQX) on the excitatory actions of the 5-HT3 receptor agonist 1-phenylbiguanide (PBG) were studied. 2. In extracellular recording experiments, PBG (0-40 nA) increased the firing rate of thirty-five of the thirty-nine neurones tested. The PBG-evoked excitation was attenuated by application of Mg2+ (1-10 nA) in sixteen of seventeen neurones or Cd2+ (2-10 nA) in seven of eight neurones tested. At these low ejection currents neither Mg2+ nor Cd2+ altered baseline firing rates and Mg2+ had no effect on the excitations evoked by DL-homocysteic acid (n = 4), NMDA (n = 4) or (AMPA; n = 2). 3. Ionophoresis of AP5 (2-10 nA), at currents which selectively inhibited NMDA-evoked excitations, attenuated PBG-evoked excitations in all eight neurones tested. DNQX (5-20 nA), at currents which selectively inhibited AMPA-evoked excitations, also attenuated PBG-evoked excitations (n = 3). 4. Intracellular activity was recorded in nine DVMN neurones. In six neurones ionophoretic application of PBG (10-200 nA) depolarized the membrane and increased firing rate whilst in the other three neurones, PBG had no effect on membrane potential though it increased synaptic noise (n = 3) and firing rate (n = 2). In all six neurones tested, ionophoresis of Mg2+ (10-120 nA) attenuated the PBG-evoked increases in synaptic noise and firing rate. 5. In conclusion, the data are consistent with the hypothesis that 5-HT3 receptor agonists activate DVMN neurones partly by acting on receptors located at sites presynaptic to the neurones. Activation of these receptors appears to facilitate release of glutamate, which, in turn, acts on postsynaptic NMDA and non-NMDA receptors to activate the neurones.
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Department of Physiology and Autonomic Neuroscience Institute, Rowland Hill Street, London NW3 2PF, UK.
Ramage
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Jordan
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005725:Ganglia, Autonomic / Q000166:cytology; D007478:Iontophoresis; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000737:chemistry* / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000737:chemistry* / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014630:Vagus Nerve / Q000166:cytology*
D001645:Biguanides; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists; D002104:Cadmium; C056723:FG 9041; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D008274:Magnesium; C008846:phenyl biguanide