P2X3 receptor antagonism reduces the occurrence of apnoeas in newborn rats

Author(s)

Katayama, Pedro Lourenco ^{[1, 2]} ; Abdala, Ana Paula ^[2] ; Charles, Ian ^[2] ; Pijacka, Wioletta ^{[2, 3]} ; Salgado, Helio Cesar ^[1] ; Gever, Joel ^[4] ; Ford, Anthony P. ^[4] ; Paton, Julian F. R. ^{[2, 5]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Physiol, Sao Paulo - Brazil

^[2] Univ Bristol, Fac Biomed Sci, Sch Physiol Pharmacol & Neurosci, Bristol CardioNom Grp, Bristol BS8 1TD, Avon - England

^[3] MedImmune Ltd, Dept Cardiovasc Renal & Metab, Granta Pk, Cambridge - England

^[4] Afferent Pharmaceut, San Mateo, CA - USA

^[5] Univ Auckland, Fac Med & Hlth Sci, Dept Physiol, Pk Rd, Auckland 1142 - New Zealand

• Document type: Journal article
• Source: Respiratory Physiology & Neurobiology; v. 277, JUN 2020.
• Web of Science Citations: 0

Abstract

Hyperreflexia of the peripheral chemoreceptors is a potential contributor of apnoeas of prematurity (AoP). Recently, it was shown that elevated P2X3 receptor expression was associated with elevated carotid body afferent sensitivity. Therefore, we tested whether P2X3 receptor antagonism would reduce AoP known to occur in newborn rats. Unrestrained whole-body plethysmography was used to record breathing and from this the frequency of apnoeas at baseline and following administration of either a P2X3 receptor antagonist - AF-454 (5 mg/ kg or 10 mg/kg s.c.) or vehicle was derived. In a separate group, we tested the effects of AF-454 (10 mg/kg) on the hypoxic ventilatory response (10 % FiO(2)). Ten but not 5 mg/kg AF-454 reduced the frequency of AoP and improved breathing regularity significantly compared to vehicle. Neither AF-454 (both 5 and 10 mg/kg) nor vehicle affected baseline respiration. However, P2X3 receptor antagonism (10 mg/kg) powerfully blunted hypoxic ventilatory response to 10 % FiO(2). These data suggest that P2X3 receptors contribute to AoP and the hypoxic ventilatory response in newborn rats but play no role in the drive to breathe at rest. (AU)

• FAPESP's process: 16/02184-0 - P2X3 receptor targeting in the carotid body for regulating hypertension: a translational perspective
• Grantee: Pedro Lourenço Katayama
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)