Nerve Growth Factor-Induced Increase in [ 3 H]Thymidine Incorporation into Pancreas of Young Rats and Its Partial Blockade by Propranolol or Partial Sialoadenectomy

Abstract

Administration of nerve growth factor (NGF) twice daily for 2 days to rats 11 days at the time of the initial injection resulted in a 6.6-fold increase in [³H]thymidine levels of pancreas, when comparison was made to levels of untreated controls. Isoproterenol (ISO), a β-adrenergic agonist known to produce marked increase in [³H]thymidine incorporation into DNA of salivary glands, caused increases in levels of [³H]thymidine in pancreas that were similar in magnitude to those induced by NGF. The combined administration of ISO and NGF did not cause any increase above those observed with either agent alone. Administration of propranolol (3 mg/kg body wt) prior to administration of ISO prevented the usual ISO-induced increase in DNA synthesis, but propranolol in either a 3- or 9-mg/kg body wt dose, caused only a 50% inhibition of NGF-induced thymidine incorporation. In the absence of the submandibular-sublingual glands, the ISO failed to induced the usual high levels of thymidine incorporation, whereas NGF induced the same high levels observed in rats with submandibular glands intact. NGF did not alter the distribution of β ₁- and β ₂-adrenoceptors in the pancreas but did increase norepinephrine when the initial administration was at age 5 days, but not when it was given at age 10 days. Since NGF increased DNA synthesis in the absence of submandibular-sublingual glands, whereas ISO did not, this suggests that ISO requires NGF to induce β ₁-activation and subsequent synthesis and that NGF is a direct activator.