The role of central 5-HT(1A) receptors in the control of B-fibre cardiac and bronchoconstrictor vagal preganglionic neurones in anaesthetized cats.
1. Experiments were performed to determine whether 5-HT(1A) receptors (a) modulate the activity of cardiac and bronchoconstrictor vagal preganglionic neurones (CVPNs and BVPNs) in the nucleus ambiguus (NA) and (b) are involved in pulmonary C-fibre afferent-evoked excitation of CVPNs, by right-atrial injections of phenylbiguanide (PBG). These experiments were carried out on alpha-chloralose-anaesthetized, artificially ventilated and atenolol (1 mg kg(-1))-pretreated cats. 2. The ionophoretic application of 8-OH-DPAT (a selective 5-HT(1A) receptor agonist) influenced the activity of 16 of the 19 CVPNs tested. 8-OH-DPAT tended to cause inhibition at low currents (40 nA) and excitation at high currents (120 nA). The activity of 15 of these neurones increased in response to the application of 8-OH-DPAT. In six of the CVPNs tested, this excitatory action of 8-OH-DPAT was attenuated by co-application of the selective 5-HT(1A) receptor antagonist WAY-100635. 3. The pulmonary C-fibre afferent-evoked excitation of eight CVPNs was attenuated by ionophoretic application of WAY-100635. 4. In three out of four CVPNs, the ionophoretic application of PBG caused excitation. 5. In five out of the nine identified BVPNs that were tested with ionophoretic application of 8-OH-DPAT, excitation was observed that was attenuated by WAY-100635. 6. WAY-100635 (I.V. or intra-cisternally) also reversed bradycardia, hypotension and the decrease in phrenic nerve activity evoked by the I.V. application of 8-OH-DPAT (42 microg kg(-1)). 7. In conclusion, the data indicate that 5-HT(1A) receptors located in the NA play an important role in the reflex activation of CVPNs and BVPNs, and support the view that overall, these receptors play a fundamental role in the reflex regulation of parasympathetic outflow.
Wang
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Department of Pharmacology, University College London, Royal Free Campus, Rowland Hill Street, Hampstead, London NW3 2PF, UK.
Ramage
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects*; D016084:Bronchoconstriction / Q000187:drug effects*; D002415:Cats; D004594:Electrophysiology; D006321:Heart / Q000294:innervation*; D007478:Iontophoresis; D008168:Lung / Q000294:innervation; D008564:Membrane Potentials / Q000502:physiology; D009412:Nerve Fibers / Q000502:physiology; D010791:Phrenic Nerve / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin