Perinatal exposure to environmental tobacco smoke induces adenylyl cyclase and alters receptor-mediated cell signaling in brain and heart of neonatal rats.
Perinatal exposure to environmental tobacco smoke (ETS) has adverse effects on neurobehavioral development. In the current study, rats were exposed to ETS during gestation, during the early neonatal period, or both. Brains and hearts were examined for alterations in adenylyl cyclase (AC) activity and for changes in beta-adrenergic and m2-muscarinic cholinergic receptors and their linkage to AC. ETS exposure elicited induction of total AC activity as monitored with the direct enzymatic stimulant, forskolin. In the brain, the specific coupling of beta-adrenergic receptors to AC was inhibited in the ETS groups, despite a normal complement of beta-receptor binding sites. In the heart, ETS evoked a decrease in m2-receptor expression. In both tissues, the effects of postnatal ETS, mimicking passive smoking, were equivalent to (AC) or greater than (m2-receptors) those seen with prenatal ETS mimicking active smoking; the effects of combined prenatal and postnatal exposure were equivalent to those seen with postnatal exposure alone. These data indicate that ETS exposure evokes changes in cell signaling that recapitulate those caused by developmental nicotine treatment. Since alterations in AC signaling are known to affect cardiorespiratory function, the present results provide a mechanistic link reinforcing the participation of ETS exposure, including postnatal ETS, in disturbances culminating in events like Sudden Infant Death Syndrome.
Slotkin
T A
TA
Department of Pharmacology & Cancer Biology, Duke University Medical Center, Box 3813, Durham, NC 27710, USA. t.slotkin@duke.edu
Pinkerton
K E
KE
Garofolo
M C
MC
Auman
J T
JT
McCook
E C
EC
Seidler
F J
FJ
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001921:Brain / Q000502:physiology*; D004781:Environmental Exposure; D004790:Enzyme Induction; D005260:Female; D006321:Heart / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction; D012906:Smoke
D011956:Receptors, Cell Surface; D012906:Smoke; D000262:Adenylyl Cyclases