Studies of a transplantable rat pheochromocytoma: biochemical characterization and catecholamine secretion.
The biochemistry and secretory characteristics of a transplantable rat pheochromocytoma have been studied. This tumor possesses the enzyme required for the biosynthesis of norepinephrine from tyrosine, and stores large amounts of norepinephrine (33 +/- 3 nmol/mg of protein). The tumor does not have detectable levels of noradrenalin N-methyltransferase, nor does it contain significant amounts of epinephrine. Approximately two-thirds of the catecholamine content, and one-half of the dopamine beta-monoxygenase activity in the tumor can be isolated in a granule fraction by sedimentation. This granule fraction also contains ATP; the molar ratio of catecholamine to ATP in this granule fraction (5.6 +/- 0.9) is similar to that found in granules prepared from normal adrenal glands. Cell suspensions were prepared by mechanical disruption of the tumor. Incubation of these cell suspensions in media containing 56 mM K+, or the divalant cation ionophores, lasolocid or A23187, leads to the release of catecholamine from these cells. The cells do not secrete catecholamine in response to acetycholine. Catecholamine release induced by 56 mM K+ appears to be by exocytosis, since this release is dependent upon extracellular Ca++, and is accompanied by the release of dopamine beta-monooxygenase, but not of lactate dehydrogenase, from the cells. The mechanism by which the ionophores stimulate catecholamine secretion has not been established.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002395:Catecholamines / Q000096:biosynthesis / Q000378:metabolism*; D002838:Chromaffin System / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism*; D010673:Pheochromocytoma / Q000201:enzymology / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013268:Stimulation, Chemical; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors
D002395:Catecholamines; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D004299:Dopamine beta-Hydroxylase; D011188:Potassium; D002118:Calcium