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• W2065596148 abstract "β2-Adrenoceptor agonists are commonly used to arrest preterm labor but they also penetrate the placenta to stimulate fetal β-adrenergic receptors (βAR), and have been implicated in subsequent neurobehavioral deficits. We administered terbutaline to pregnant rats on gestational days (GD) 17–20 and during two postnatal (PN) periods, PN2–5 and PN11–14, that correspond to third trimester human neurological development. We then examined βAR binding sites and adenylyl cyclase (AC) signaling in fetal brain or neonatal brain regions. Although fetal terbutaline administration evoked βAR downregulation, the ability of isoproterenol to stimulate AC was enhanced instead of desensitized. Sensitization occurred at post-receptor signaling proteins, as augmented responses were also seen for stimulants that bypass the receptors to work on G-proteins (NaF) or that stimulate AC directly (forskolin and Mn2+). When terbutaline was given on PN2–5, βAR downregulation was obtained in brainstem, forebrain and cerebellum, but desensitization of the AC response was seen only in the forebrain; the desensitization was heterologous, reflecting decrements in total AC activity rather than specific loss of the βAR response. With treatment on PN11–14, only the cerebellum showed βAR downregulation and induction at the level of post-receptor signaling proteins maintained the βAR-mediated AC response. Our results indicate that, unlike the adult, βAR signaling in the fetus and neonate is resistant to homologous desensitization by β-agonists, and in fact, displays heterologous sensitization that sustains or enhances the overall response. The inability to desensitize βAR responses may lead to disruption of neural cell development as a consequence of tocolytic therapy." @default.
• W2065596148 created "2016-06-24" @default.
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• W2065596148 date "2001-11-01" @default.
• W2065596148 modified "2023-10-16" @default.
• W2065596148 title "β-Adrenoceptor signaling in the developing brain: sensitization or desensitization in response to terbutaline" @default.
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• W2065596148 doi "https://doi.org/10.1016/s0165-3806(01)00282-6" @default.
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