Biomaterial Database

TPA (12-O-tetradecanoylphorbol-13-acetate) enhances the central hypoglycemic action of thyrotropin-releasing hormone in mice. 1988

S Amir

Department of Psychology, Concordia University, Montreal, Que., Canada.

This study examined the effect of the calcium- and phospholipid-dependent protein kinase C (PKC) activator, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the plasma glucose responses to central thyrotropin-releasing hormone (TRH) injection in mice in order to evaluate the involvement of PKC in the mechanism of TRH action in the central nervous system (CNS). TRH (0.1-10 micrograms), as well as the neuroactive TRH analogs, CG 3509, CG 3703, DN 1417, RX 77368, [Nva2]-TRH, KPC-TRH, and TRH-Gly (0.1-10 micrograms), injected centrally in normoglycemic mice reduced the circulating glucose levels in a dose-dependent manner. TPA (0.1-1 microgram), administered centrally together with TRH (1 microgram) or the TRH analogs strongly enhanced the hypoglycemic response. Similar doses of TPA had no effect on plasma glucose when administered alone or together with TRH analogs devoid of central hypoglycemic action, i.e. [Glu1]-TRH, [Phe2]-TRH, and [Gly3]-TRH (1 microgram). Central injection of a TPA analog lacking PKC-stimulating activity, 4-alpha-phorbol (0.1-1 microgram) had no effect on the hypoglycemic response to coadministered TRH. These results, demonstrating a specific effect of TPA in enhancing the hypoglycemic response to central TRH or its neuroactive, though not inactive, analogs are consistent with a possible role for PKC in the mechanism of TRH action in the CNS.

UI	MeSH Term	Description	Entries
D007003	Hypoglycemia	A syndrome of abnormally low BLOOD GLUCOSE level. Clinical hypoglycemia has diverse etiologies. Severe hypoglycemia eventually lead to glucose deprivation of the CENTRAL NERVOUS SYSTEM resulting in HUNGER; SWEATING; PARESTHESIA; impaired mental function; SEIZURES; COMA; and even DEATH.	Fasting Hypoglycemia,Postabsorptive Hypoglycemia,Postprandial Hypoglycemia,Reactive Hypoglycemia,Hypoglycemia, Fasting,Hypoglycemia, Postabsorptive,Hypoglycemia, Postprandial,Hypoglycemia, Reactive
D007276	Injections, Intraventricular	Injections into the cerebral ventricles.	Intraventricular Injections,Injection, Intraventricular,Intraventricular Injection
D008297	Male		Males
D008813	Mice, Inbred ICR	An inbred strain of mouse that is used as a general purpose research strain, for therapeutic drug testing, and for the genetic analysis of CARCINOGEN-induced COLON CANCER.	Mice, Inbred ICRC,Mice, ICR,Mouse, ICR,Mouse, Inbred ICR,Mouse, Inbred ICRC,ICR Mice,ICR Mice, Inbred,ICR Mouse,ICR Mouse, Inbred,ICRC Mice, Inbred,ICRC Mouse, Inbred,Inbred ICR Mice,Inbred ICR Mouse,Inbred ICRC Mice,Inbred ICRC Mouse
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
D001786	Blood Glucose	Glucose in blood.	Blood Sugar,Glucose, Blood,Sugar, Blood
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
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