Induction of DNA Synthesis in Cultured Rat Hepatocytes Through Stimulation of α ₁ Adrenoreceptor by Norepinephrine

Abstract

Addition of norepinephrine to primary cultures of adult rat hepatocytes stimulates the incorporation of [3H]thymidine in a dose-dependent manner. This effect has been observed in serum-free medium containing epidermal growth factor and insulin. Stimulation of DNA synthesis by norepinephrine was strongly antagonized by the alpha 1-adrenergic antagonist prazosin but not by an alpha 2 antagonist or by a beta-adrenergic blocker. The beta agonist isoproterenol did not stimulate significant DNA synthesis. These results indicate that catecholamines interact with the alpha 1 adrenoreceptor to stimulate DNA synthesis in hepatocytes. Since alpha 1 receptors are present in most cells, this receptor may be important in cell growth regulation.

Screening for candidate hepatic growth factors by selective portal infusion after canine Eck's fistula

“…TGF-a is a stronger mitogen than EGF for hepatocytes in vitro (23), and in many other functions besides hepatocyte replication it is a stronger affector (24). Other putative stimulators that had little or no effect in Eck's fistula preparation included the hormones prolactin (25), angiotensin II (26), vasopressin (7), norepinephrine (6,27), estradiol (28) and glucagon (29).…”

“…) Regulation of liver mass and the control of hepatic regeneration are poorly understood and presumably related processes. Hormones, soluble mediators and other substances that can influence hepatocyte size, proliferation or both have been identified with in vitro or in vivo models of testing (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Both test systems are important because no assurance exists that agents with in vitro activity are physiologically important.…”

Frequent reduced expression of alpha-1B-adrenergic receptor caused by aberrant promoter methylation in gastric cancers

“…Furthermore, in gastric cancers, the ADRA1B promoter was very frequently methylated, generally in association with reduced ADRA1B expression. Alpha1-adrenergic receptors are members of the superfamily of G protein-coupled receptors and mediate effects related to the regulation of cellular hypertrophy and proliferation (Cruise et al, 1985;Lefkowitz and Caron, 1988;Cotecchia et al, 1990;Thonberg et al, 1994;Spector et al, 1997). Three distinct subtypes of alpha1-adrenergic receptors (alpha1A-(ADRA1A), alpha1B-(ADRA1B), and alpha1D-(ADRA1D) adrenergic receptors) have a prominent role in cell growth, and activation of ADRA1A and ADRA1B inhibits serum-prompted cell proliferation (Auer et al, 1998;Shibata et al, 2003).…”

Screening for candidate hepatic growth factors by selective portal infusion after canine Eck’s fistula

“…TGF-α is a stronger mitogen than EGF for hepatocytes in vitro (23), and in many other functions besides hepatocyte replication it is a stronger affector (24). Other putative stimulators that had little or no effect in Eck's fistula preparation included the hormones prolactin (25), angiotensin II (26), vasopressin (7), norepinephrine (6,27), estradiol (28) and glucagon (29).…”