Activation of Tyrosine Hydroxylase by Nicotine in Rat Adrenal Gland

Abstract

The administration of nicotine activates tyrosine hydroxylase in the rat adrenal gland. This activation is apparently maximal 25 min after a single subcutaneous injection of nicotine at 2.3 mg/kg. Repeated injections of nicotine (seven injections once every 30 min) are associated with a persistent activation of adrenal tyrosine hydroxylase for at least 3 h. The nicotinic receptor antagonist hexamethonium does not significantly inhibit the nicotine-mediated activation of tyrosine hydroxylase in innervated adrenal glands. However, hexamethonium completely blocks the activation of adrenal tyrosine hydroxylase by nicotine in denervated adrenal glands. Furthermore, even though a single injection of nicotine activates tyrosine hydroxylase in both innervated and denervated adrenal glands, repeated injections of nicotine do not activate tyrosine hydroxylase in denervated adrenal glands. Our results suggest that the systemic administration of nicotine activates adrenal tyrosine hydroxylase by two mechanisms: (1) via direct interaction with adrenal chromaffin cell nicotinic receptors; and (2) via stimulation of the CNS leading to the release from the splanchnic nerve of substances that interact with adrenal chromaffin cell receptors other than the nicotinic receptor.

Regulation of Tyrosine Hydroxylase mRNA Stability by Protein-binding, Pyrimidine-rich Sequence in the 3′-Untranslated Region

“…It is enhanced during differentiation of neuroblastoma cells (1) and during stimulation of the protein kinase C pathway in PC12 cells (2). In contrast, the stability of TH mRNA does not change in PC12 cells during stimulation of TH mRNA expression by dexamethasone or forskolin (3). A recent study demonstrated substantial differences in basal TH mRNA turnover rates between different neuronal populations from as short a time as 6 -7 h, in the dopaminergic neurons of the arcuate nucleus, to as long as 11-23 h, in the dopaminergic midhypothalamic neurons (4).…”

“…Recently, there has been growing evidence that TH mRNA is also regulated at the level of mRNA stability. TH mRNA is a stable message with a half-life that varies from 9 to 16 h in various subclones of PC12 cells (1)(2)(3). It is enhanced during differentiation of neuroblastoma cells (1) and during stimulation of the protein kinase C pathway in PC12 cells (2).…”

Expression of mRNA coding for four catecholamine-synthesizing enzymes in human adrenal pheochromocytomas

“…A variety of factors, including neural impulses, have been reported to regulate the TH gene expression in adrenal medullary cells (8)(9)(10). The expression of the TH gene has also been studied in rat pheochromocytoma cell lines (11)(12)(13).…”

Regulation of Tyrosine Hydroxylase Gene Expression by Muscarinic Agonists in Rat Adrenal Medulla

“…The increases in adrenal TH protein elicited by these stimuli are usually preceded by induction of TH mRNA and stimulation of TH gene transcription rate (Tank et al, 1985;Faucon Biguet et al, 1986;Fossom et al, 1991a;Osterhout et al, 1997). These responses are also usually dependent on presynaptic innervation of the adrenal medulla and hence are mediated by transsynaptic mechanisms Kvetnansky et al, 1971;Fluharty et al, 1983;Stachowiak et al, 1985Stachowiak et al, , 1986.…”

“…Tyrosine hydroxylase (TH) is induced in the adrenal medulla following several different stimuli, including prolonged stress (Kvetnansky et al, 1970;Thoenen, 1970;Kvetnansky and Sabban, 1993), treatment with catecholamine-depleting drugs, like reserpine Thoenen et al, 1969), chronic electroconvulsive shock (Masserano et al, 1981), and treatment with nicotine (Fossom et al, 1991a;Hiremagalur and Sabban, 1995;Jahng et al, 1997). The increases in adrenal TH protein elicited by these stimuli are usually preceded by induction of TH mRNA and stimulation of TH gene transcription rate (Tank et al, 1985;Faucon Biguet et al, 1986;Fossom et al, 1991a;Osterhout et al, 1997).…”