title: Sensory afferent selective role of P2 receptors in the nucleus tractus solitarii for mediating the cardiac component of the peripheral chemoreceptor reflex in rats.
abstract: We have assessed the functional role of type 2 purinergic (P2) receptors within the caudal aspect of the commissural nucleus tractus solitarii (NTS) in mediating the peripheral chemoreceptor reflex cardiorespiratory response in the arterially perfused in situ working heart-brainstem preparation of rats. Microinjection in NTS of either suramin (100 pmol) or pyrinoxalphosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium salt (PPADS; 10 pmol) depressed the reflex bradycardia (by approximately 50 %), but not the tachypnoea, following peripheral chemoreceptor stimulation. In contrast, the reflex bradycardia produced by stimulation of pharyngo-oesophageal receptors was unaffected. Furthermore, microinjections in NTS of the P2X receptor agonist alpha,beta-methyleneadenosine 5'-triphosphate (10 pmol) evoked a bradycardia which was antagonized by suramin (100 pmol). This P2X agonist reversibly potentiated the peripheral chemoreceptor-evoked bradycardia. The effect of suramin was selective to purinergic receptors because the bradycardia evoked by microinjection of alpha,beta-methyleneadenosine 5'-triphosphate was blocked while the bradycardic responses to microinjections of NMDA or non-NMDA receptor agonists were not affected. From whole-cell recordings, some NTS neurones received convergent excitatory synaptic inputs from both peripheral chemoreceptors and receptors at the pharyngo-oesophageal junction. The excitatory postsynaptic response evoked by chemoreceptor stimulation was depressed by suramin, but convergent excitatory inputs from pharyngo-oesophageal receptors were unperturbed. Our findings support the hypothesis that caudal commissural NTS P2 purinergic receptors play a role in the neurotransmission of the parasympathetic (bradycardic) component of the chemoreceptor reflex. This effect is highly selective in that the chemoreceptor afferent-evoked tachypnoea, as well as other visceral receptor-mediated reflex bradycardia, remain unaffected.
authors.affiliation: Department of Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 2TD, UK. julian.f.r.paton@bris.ac.uk
authors.forename: Julian F R
authors.initials: JF
authors.lastname: Paton
authors.forename: Patrícia M
authors.initials: PM
authors.lastname: De Paula
authors.forename: K Michael
authors.initials: KM
authors.lastname: Spyer
authors.forename: Benedito H
authors.initials: BH
authors.lastname: Machado
authors.forename: Pedro
authors.initials: P
authors.lastname: Boscan
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001919:Bradycardia / Q000503:physiopathology; D002628:Chemoreceptor Cells / Q000502:physiology*; D006321:Heart / Q000294:innervation* / Q000502:physiology; D008845:Microinjections; D009475:Neurons, Afferent / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D017552:Solitary Nucleus / Q000166:cytology / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D013569:Synapses / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin