Sensory afferent selective role of P2 receptors in the nucleus tractus solitarii for mediating the cardiac component of the peripheral chemoreceptor reflex in rats.
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.
Paton
Julian F R
JF
Department of Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 2TD, UK. julian.f.r.paton@bris.ac.uk
De Paula
Patrícia M
PM
Spyer
K Michael
KM
Machado
Benedito H
BH
Boscan
Pedro
P
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
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