Nerve growth factor-induced increase in [3H]thymidine incorporation into parotid and submandibular glands of young rats and its partial blockade by propranolol or partial sialoadenectomy.
Administration of nerve growth factor (NGF) twice daily for 2 days to young rats (11 days old at the time of the initial injection) resulted in an 8.1-fold increase in [3H]thymidine levels of the parotid gland, and a 9.7-fold increase in levels of the submandibular gland when compared to untreated controls. Isoproterenol (ISO), a beta-adrenergic receptor agonist, caused an 8.7-fold increase in [3H]thymidine incorporation into DNA of the parotid gland, and a 10.7-fold increase in [3H]thymidine in the submandibular gland when compared to controls. The increase in thymidine was accompanied by parotid gland enlargement as well as an increase in cell surface beta 1-4 galactosyltransferase, an enzyme whose expression has been associated previously with acinar cell proliferation. Administration of NGF and ISO together were not additive in their effects on the parotid and submandibular glands. The introduction of propranolol, a beta-adrenergic receptor antagonist, completely negated the ISO effects on the salivary glands but was only partially effective in blocking the NGF effects on the glands. An assay of parotid levels of norepinephrine showed NGF treatment to cause an increase in gland-associated levels of neurotransmitter. Removal of the submandibular/sublingual glands prior to administration of ISO prevented the above changes in the parotid gland. NGF administered to partially sialoadenectomized rats was also less effective in inducing parotid gland hypertrophy and hyperplasia. Simultaneous administration of NGF and ISO to the partially sialoadenectomized rats had an additive influence on [3H]thymidine incorporation, galactosyltransferase expression and gland hypertrophy. The results suggest that NGF influences salivary gland cell growth in part through activation of cell-surface beta-adrenergic receptors.
Schneyer
C A
CA
Department of Physiology and Biophysics, University of Alabama, Birmingham 35294.
Humphreys-Beher
M G
MG
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D004247:DNA / Q000096:biosynthesis*; D007545:Isoproterenol / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D012469:Salivary Glands / Q000601:surgery; D013361:Sublingual Gland / Q000601:surgery; D013363:Submandibular Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery; D013936:Thymidine / Q000378:metabolism; D006022:beta-N-Acetylglucosaminylglycopeptide beta-1,4-Galactosyltransferase / Q000378:metabolism
D009414:Nerve Growth Factors; D004247:DNA; D011433:Propranolol; D006022:beta-N-Acetylglucosaminylglycopeptide beta-1,4-Galactosyltransferase; D007545:Isoproterenol; D013936:Thymidine; D009638:Norepinephrine