Induction of tyrosine hydroxylase and neuropeptide Y by carbachol: Modulation with age

With aging, circulating catecholamines are elevated in both humans and anim als. This may be related to the increased basal levels of dopamine beta-hyd roxylase (DPH) and tyrosine hydroxylase (TH) mRNA levels and TH enzyme acti vity in the adrenal medulla of senescent compared with younger animals. Col d exposure induces TH and D beta H mRNA, and the cholinergic pathway is bel ieved to be involved in the cold-stimulated increase in Tli expression in t he adrenal medulla. However, TH gene expression in the senescent rat is res istant to stimulation by cold exposure, suggesting that the cholinergic pat hway may be impaired with age in the adrenal medulla. To investigate this p ossibility we administered carbachol (0.5 mg/kg ip, every 12 hours for 3 co nsecutive days), a mired nicotinic-muscarinic agonist, to young (4-month-ol d) and senescent (24-month-old) male F-344 rats. We examined the induction of TH mRNA, TH immunoreactivity, and TH enzyme activity in the adrenal medu lla in young and old rats. In addition D beta H and NPY mRNA levels were de termined in the adrenal medulla with or without carbachol administration. B asal levels of TH mRNA, TH immunoreactivity, and TH activity as well II as D beta H and neuropeptide Y (NPY) mRNA were 1.5- to I-fold greater in the a drenal medullae of old rats compared with young rats. Carbachol administrat ion increased TH mRNA, TH immunoreactivity ; and TH activity as well as D b eta H and NPY mRNA to the same or a greater extent in the senescent compare d with the young rats. The present study indicates that the cholinergic ind uction of TH or D beta H are not impaired,with age, and that senescent rats retain the capacity to respond to carbachol stimulation. The present findi ngs cannot explain why the adrenal medullae from senescent rats are resista nt to the cold-induced elevation of TH mRNA and TH activity observed in you ng rats.