Selective linkage of beta-adrenergic receptors to functional responses in developing rat lung and liver: phosphatidic acid phosphatase, ornithine decarboxylase and lung liquid reabsorption.
Neurotransmitter receptors may exhibit transient linkage to specific developmental processes involved in physiological adaptation to extrauterine life and in cell maturation. We have examined the responsiveness of the developing rat lung to beta-adrenergic agonists, using fluid reabsorption, phosphatidic acid phosphatase (an enzyme involved in surfactant synthesis) and ornithine decarboxylase (an enzyme related to cellular development) as markers of these activities. The ability of beta-adrenergic agonists to stimulate phosphatidic acid phosphatase and to cause liquid reabsorption first appeared just before birth, a period in which few receptor binding sites are present; the reactivity of both these processes declined after birth, but the enzymatic stimulation reached a second peak of response during the second and third postnatal weeks. The ability of beta-adrenergic challenge to elicit stimulation of lung phosphatidic acid phosphatase then declined into adulthood, despite the fact that receptor binding sites are increasing during the same period. Lung ornithine decarboxylase activity was poorly linked to beta-receptors in the immediate perinatal period and reached a peak of reactivity during the late postnatal period in which the coupling to phosphatidic acid phosphatase was lost. The pattern for phosphatidic acid phosphatase and liquid content was selective for the lung, as no stimulatory effects were seen for these variables in the liver, despite the comparable beta-adrenergic effects on ornithine decarboxylase in the two tissues. These data suggest that, during development, the coupling of receptors to specific cellular events is more important than the number of receptor sites in determining the pattern of physiological and cellular responses mediated by neurotransmitters.(ABSTRACT TRUNCATED AT 250 WORDS)
Kudlacz
E M
EM
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Navarro
H A
HA
Eylers
J P
JP
Dobbins
S S
SS
Lappi
S E
SE
Slotkin
T A
TA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D009929:Organ Size; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010711:Phosphatidate Phosphatase / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013726:Terbutaline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D010744:Phosphoric Monoester Hydrolases; D010711:Phosphatidate Phosphatase; D009955:Ornithine Decarboxylase; D007545:Isoproterenol; D013726:Terbutaline