brl-37344 and Endocrine-Gland-Neoplasms

1. The adrenoceptor in a mouse pineal gland tumour cell line (PGT-beta) was identified and characterized using pharmacological and physiological approaches. 2. Adrenaline and noradrenaline, adrenoceptor agonists, stimulated cyclic AMP generation in a concentration-dependent manner, but had no effect on inositol 1,4,5-trisphosphate production. Adrenaline was a more potent activator of cyclic AMP generation than noradrenaline, with half maximal-effective concentrations (EC50) seen at 175+/-22 nM and 18+/-2 microM for adrenaline and noradrenaline, respectively. 3. The addition of forskolin synergistically stimulated the adrenaline-mediated cyclic AMP generation in a concentration-dependent manner. 4. The pA2 value for the specific beta2-adrenoceptor antagonist ICI-118,551 (8.7+/-0.4) as an antagonist of the adrenaline-stimulated cyclic AMP generation were 3 units higher than the value for the betaI-adrenoceptor antagonist atenolol (5.6+/-0.3). 5. Treatment of the cells with adrenaline and forskolin evoked a 3 fold increase in the activity of serotonin N-acetyltransferase with the peak occurring 6 h after stimulation. 6. These results suggest the presence of beta2-adrenoceptors in mouse pineal cells and a functional relationship between the adenylyl cyclase system and the regulation of N-acetyltransferase expression.

Topics: Adenylyl Cyclases; Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Arylamine N-Acetyltransferase; Calcium; Colforsin; Cyclic AMP; Cytosol; Dose-Response Relationship, Drug; Drug Synergism; Endocrine Gland Neoplasms; Enzyme Activation; Epinephrine; Ethanolamines; Mice; Norepinephrine; Pineal Gland; Propanolamines; Receptors, Adrenergic, beta-2; Tumor Cells, Cultured