We have investigated the simultaneous regulation of cell surface distribution and ligand binding of the asialoglycoprotein (ASGP) receptor and the transferrin receptor in a hepatoma cell line by phorbol esters. One hour exposure to phorbol esters causes a redistribution of both receptors to the cell interior as shown by radioligand binding at 4 degrees C and selective immunoprecipitation from t...

The focus of my research has been on understanding the initial events in phorbol ester action. The phorbol esters are natural products derived from Croton tiglium, the source of croton oil, and from other plants of the family Euphorbiaceae (1). The phorbol esters initially became the object of intense research interest on the basis of their potent activity as mouse skin tumor promoters (2). The...

The focus of my research has been on understanding the initial events in phorbol ester action. The phorbol esters are natural products derived from Croton tiglium, the source of croton oil, and from other plants of the family Euphorbiaceae (1). The phorbol esters initially became the object of intense research interest on the basis of their potent activity as mouse skin tumor promoters (2). The...

Parathyroid hormone (PTH) increased intracellular cyclic AMP and reduces Na+/phosphate cotransport activity in OK cells [Malmström & Murer (1986) Am. J. Physiol. 251, C23-C31; Caverzasio, Rizzoli & Bonjour (1986) J. Biol. Chem. 261, 3233-3237]. It was also shown that PTH activates phosphoinositide metabolism in OK cells [Hruska, Moskowitz, Esprit, Civitelli, Westbrook & Huskey (1987) J. Clin. I...

been pretreated with a single subthreshold dose of a carcin ogen (2, 6, 9, 44). If either treatment is omitted or if the order of treatments is reversed, no tumors result. On the other hand, delay of up to a year between exposure to the carcinogen and the subsequent exposure to the phorbob derivative do not prevent tumor appearance. The reversibil ity of the action of the phorbol esters and the...

The effects of tumour-promoting phorbol esters on the receptor-mediated endocytosis of insulin were investigated in the human hepatoma cell line HepG2. Treatment of these cells with the biologically active phorbol 12-O-tetradecanoylphorbol 13-acetate (TPA), but not with the non-tumour-promoting analogue 4 alpha-phorbol 12,13-didecanoate, resulted in dramatic morphological changes, which were ac...

Bovine adrenal chromaffin cells were exposed to phorbol esters to determine the effects of reduced levels of protein kinase C on secretion of hormones. Treatment with active phorbol esters such as 4 beta-phorbol 12, 13-didecanoate (PDD) reduced levels of protein kinase C activity with a maximal 80-90% reduction in activity after 16-24 h treatment (greater than or equal to 500 nM PDD). Treatment...

Muscarinic receptor stimulation in the hippocampus has been associated with inositol phospholipid breakdown. In other systems this leads to the formation of inositol trisphosphate and diacylglycerol, which promotes the activation of protein kinase C. Phorbol esters, which directly activate protein kinase C, exhibit high and specific binding in the hippocampus. This, along with the advantages of...

Phorbol esters increase prolactin synthesis and release and inhibit growth hormone production by GH4Ci cells, a clonal strain of rat pituitary cells. We examined the actions of phorbol esters on the binding of peptides that regulate the function of GH4C, cells and found that phorbol esters decreased the specific binding of epidermal growth factor (EGF), thyrotropinreleasing hormone (TRH), and s...

Palmitoylcarnitine, a reported protein kinase C inhibitor, enhanced the phorbol ester dependency of the enzyme, augmenting protein kinase C activity in the presence of phorbol esters such as phorbol 12,13-dibutyrate while inhibiting the basal activity measured in the presence of calcium plus phosphatidylserine. Weakly potent phorbol esters such as phorbol 12,13-diacetate and 4-O-methylphorbol 1...