Noradrenergic modulation of respiratory motor output during tadpole development: Role of α-adrenoceptors

Abstract

Noradrenaline (NA) is an important modulator of respiratory activity. Results from in vitro studies using immature rodents suggest that the effects exerted by NA change during development, but these investigations have been limited to neonatal stages. To address this issue, we used in vitro brainstem preparations of an ectotherm, Rana catesbeiana, at three developmental stages: premetamorphic tadpoles, metamorphic tadpoles and fully mature adult bullfrogs. We first compared the effects of NA bath application (0.02-10 μmol l -1) on brainstem preparations from both pre-metamorphic (Taylor-Köllros stages VII-XI) and metamorphic tadpoles (TK stages XVIII-XXIII) and adult frogs. The fictive lung ventilation frequency response to NA application was both dose- and stage-dependent. Although no net change was observed in the pre-metamorphic group, NA application decreased fictive lung burst frequency in preparations from more mature animals. These effects were attenuated by application of α-adrenoceptor antagonists. Conversely, NA application elicited dose- and stage-dependent increases in fictive buccal ventilation frequency. We then assessed the contribution of α- adrenoceptors towards these responses by applying specific agonists (α1: phenylephrine; α2: clonidine; concentration range from 10 to 200 μmol l-1 for both). Of the two agonists used, only phenylephrine application consistently mimicked the lung burst frequency response observed during NA application in each stage group. However, both agonists decreased buccal burst frequency, thus suggesting that other (β) adrenoceptor types mediate this response. We conclude that modulation of both buccal and lung-related motor outputs change during development. NA modulation affects both types of respiratory activities in a distinct fashion, owing to the different adrenoceptor type involved.