Fetal nicotine exposure produces postnatal up-regulation of adenylate cyclase activity in peripheral tissues.
Gestational exposure to nicotine has been shown to affect development of noradrenergic activity in both the central and peripheral nervous systems. In the current study, pregnant rats received nicotine infusions of 6 mg/kg/day throughout gestation, administered by osmotic minipump implants. After birth, offspring of the nicotine-infused dams exhibited marked increases in basal adenylate cyclase activity in membranes prepared from kidney and heart, as well as supersensitivity to stimulation by either a beta-adrenergic agonist, isoproterenol, or by forskolin. The altered responses were not accompanied by up-regulation of beta-adrenergic receptors: in fact, [125I]pindolol binding was significantly decreased in the nicotine group. These results indicate that fetal nicotine exposure affects enzymes involved in membrane receptor signal transduction, leading to altered responsiveness independently of changes at the receptor level.
Slotkin
T A
TA
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Navarro
H A
HA
McCook
E C
EC
Seidler
F J
FJ
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D009538:Nicotine / Q000494:pharmacology* / Q000633:toxicity; D010869:Pindolol / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015854:Up-Regulation
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D009538:Nicotine; D010869:Pindolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol