Il-1β and prostaglandin E 2 attenuate the hypercapnic as well as the hypoxic respiratory response via prostaglandin E receptor type 3 in neonatal mice

• Published in: Journal of applied physiology (1985) 2014-11, Vol.117 (9), p.1027-1036
• Main Authors: Siljehav, Veronica, Shvarev, Yuri, Herlenius, Eric
• Format: Article
• Language: English
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00542.2014

Prostaglandin E 2 (PGE 2 ) serves as a critical mediator of hypoxia, infection, and apnea in term and preterm babies. We hypothesized that the prostaglandin E receptor type 3 (EP3R) is the receptor responsible for PGE 2 -induced apneas. Plethysmographic recordings revealed that IL-1β (ip) attenuated the hypercapnic response in C57BL/6J wild-type (WT) but not in neonatal (P9) EP3R −/− mice ( P < 0.05). The hypercapnic responses in brain stem spinal cord en bloc preparations also differed depending on EP3R expression whereby the response was attenuated in EP3R −/− preparations ( P < 0.05). After severe hypoxic exposure in vivo, IL-1β prolonged time to autoresuscitation in WT but not in EP3R −/− mice. Moreover, during severe hypoxic stress EP3R −/− mice had an increased gasping duration ( P < 0.01) as well as number of gasps ( P < 0.01), irrespective of intraperitoneal treatment, compared with WT mice. Furthermore, EP3R −/− mice exhibited longer hyperpneic breathing efforts when exposed to severe hypoxia ( P < 0.01). This was then followed by a longer period of secondary apnea before autoresuscitation occurred in EP3R −/− mice ( P < 0.05). In vitro, EP3R −/− brain stem spinal cord preparations had a prolonged respiratory burst activity during severe hypoxia accompanied by a prolonged neuronal arrest during recovery in oxygenated medium ( P < 0.05). In conclusion, PGE 2 exerts its effects on respiration via EP3R activation that attenuates the respiratory response to hypercapnia as well as severe hypoxia. Modulation of the EP3R may serve as a potential therapeutic target for treatment of inflammatory and hypoxic-induced detrimental apneas and respiratory disorders in neonates.