Biomaterial Database

Relationship between biological responsiveness to phorbol esters and receptor levels in GH4C1 rat pituitary cells. 1981

S Jaken, and A H Tashjian, and P M Blumberg

During a 24-hr incubation of GH4C1 cells with phorbol esters or thyrotropin-releasing hormone, there is a decrease in the number of phorbol esters receptors (down-modulation). The purpose of this study was to investigate whether this decrease in receptor number attenuated cellular responsiveness to subsequent challenge with phorbol esters. Accordingly, cellular sensitivity to a phorbol ester-mediated biological response, namely the decrease in binding of epidermal growth factor, was compared in control and down-modulated cells. This phorbol ester-mediated event is closely associated with phorbol ester receptor occupancy, and it is therefore an effect for which altered dose-response characteristics correlating with alterations in the number of phorbol ester receptors could be anticipated. In fact, during a 48-hr exposure to phorbol esters, GH4C1 cells become refractory to the effect on epidermal growth factor binding. This time course is similar to that for the loss of phorbol ester receptors. However, when cells are down modulated by pretreatment with phorbol ester or thyrotropin-releasing hormone and then (re)challenged with phorbol ester, no differences in dose-response characteristics were observed between control and down-modulated cells. We therefore conclude that phorbol ester receptor down-modulation does not affect cellular responsiveness to phorbol esters, at least when decreased epidermal growth factor binding is used as the marker for the phorbol ester-mediated event.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D010703	Phorbol Esters	Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.	Phorbol Diester,Phorbol Ester,Phorbol Diesters,Diester, Phorbol,Diesters, Phorbol,Ester, Phorbol,Esters, Phorbol
D010704	Phorbols	The parent alcohol of the tumor promoting compounds from CROTON OIL (Croton tiglium).	Tigliane,Tiglianes
D011493	Protein Kinase C	An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.	Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011955	Receptors, Drug	Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.	Drug Receptors,Drug Receptor,Receptor, Drug
D011956	Receptors, Cell Surface	Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.	Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002352	Carrier Proteins	Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes.	Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D004815	Epidermal Growth Factor	A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.	EGF,Epidermal Growth Factor-Urogastrone,Urogastrone,Human Urinary Gastric Inhibitor,beta-Urogastrone,Growth Factor, Epidermal,Growth Factor-Urogastrone, Epidermal,beta Urogastrone
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013973	Thyrotropin-Releasing Hormone	A tripeptide that stimulates the release of THYROTROPIN and PROLACTIN. It is synthesized by the neurons in the PARAVENTRICULAR NUCLEUS of the HYPOTHALAMUS. After being released into the pituitary portal circulation, TRH (was called TRF) stimulates the release of TSH and PRL from the ANTERIOR PITUITARY GLAND.	Protirelin,Thyroliberin,Abbott-38579,Antepan,Proterelin Tartrate,Proterelin Tartrate Hydrate,Protirelin Tartrate (1:1),Relefact TRH,Stimu-TSH,TRH Ferring,TRH Prem,Thypinone,Thyroliberin TRH Merck,Thyrotropin-Releasing Factor,Thyrotropin-Releasing Hormone Tartrate,Abbott 38579,Abbott38579,Hydrate, Proterelin Tartrate,Prem, TRH,Stimu TSH,StimuTSH,TRH, Relefact,Tartrate Hydrate, Proterelin,Thyrotropin Releasing Factor,Thyrotropin Releasing Hormone,Thyrotropin Releasing Hormone Tartrate