Biomaterial Database

Direct stimulation of cortisol secretion from the human NCI H295 adrenocortical cell line by vasoactive intestinal polypeptide. 1997

V J Cobb, and B C Williams, and J I Mason, and S W Walker

Department of Clinical Biochemistry, University of Edinburgh, Scotland, UK.

OBJECTIVE To investigate a possible direct action of vasoactive intestinal polypeptide (VIP) on adrenal cortisol secretion and to define its mechanism of action. METHODS The human adrenocortical carcinoma cell line NCI H295, which is not contaminated by medullary chromaffin cells, was used to aid distinction between a direct action of VIP on adrenocortical cells and an indirect mechanism involving VIP-stimulated release of catecholamines. METHODS NCI H295 cells were challenged with 10(-11)-10(-7) mol/l VIP for 4 h, with or without prior exposure for 72 h to 10 micromol/l forskolin. Cortisol and cyclic AMP contents of the overlying media were measured using in-house radioimmunoassays. Cells were treated with 10(-8)-10(-6) mol/l adrenaline or 3.3 x 10(-8) mol/l VIP with and without 10(-8)-10(-6) mol/l propranolol to exclude the possibility that an indirect mechanism of action involving beta-adrenoceptors was operating. RESULTS VIP treatment produced an increase in cortisol secretion without pre-incubation, but this was markedly enhanced by prior exposure of cells to forskolin. VIP was potent, with a threshold of 10(-11) mol/l (n = 4), reaching a maximum 3.9+/-0.9-fold increase in effect on cells pre-exposed to forskolin (n = 4) by 3.3 x 10(-8) mol/l. This increase matched the 4 h response to 10 micromol/l forskolin. Cortisol secretion was accompanied by a parallel, dose-dependent increase in accumulation of cAMP. CONCLUSIONS VIP potently and directly stimulates secretion of cortisol from these adrenocortical cells of human origin via an adenylate cyclase-coupled VIP receptor. These findings raise the possibility of a significant and direct effect of VIP in the control of steroid secretion from the adrenal cortex in humans.

UI	MeSH Term	Description	Entries
D011433	Propranolol	A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.	Dexpropranolol,AY-20694,Anaprilin,Anapriline,Avlocardyl,Betadren,Dociton,Inderal,Obsidan,Obzidan,Propanolol,Propranolol Hydrochloride,Rexigen,AY 20694,AY20694,Hydrochloride, Propranolol
D011863	Radioimmunoassay	Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.	Radioimmunoassays
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
D005576	Colforsin	Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.	Coleonol,Forskolin,N,N-Dimethyl-beta-alanine-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho(2,1-b)pyran-6-yl Ester HCl,NKH 477,NKH-477,NKH477
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006854	Hydrocortisone	The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.	Cortef,Cortisol,Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-,11-Epicortisol,Cortifair,Cortril,Epicortisol,Hydrocortisone, (11 alpha)-Isomer,Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer,11 Epicortisol
D000242	Cyclic AMP	An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.	Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000306	Adrenal Cortex Neoplasms	Tumors or cancers of the ADRENAL CORTEX.	Adrenocortical Cancer,Cancer of Adrenal Cortex,Adrenal Cortex Cancer,Cancer of the Adrenal Cortex,Neoplasms, Adrenal Cortex,Adrenal Cortex Cancers,Adrenal Cortex Neoplasm,Adrenocortical Cancers,Cancer, Adrenal Cortex,Cancer, Adrenocortical,Cancers, Adrenal Cortex,Cancers, Adrenocortical,Neoplasm, Adrenal Cortex
D000319	Adrenergic beta-Antagonists	Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.	Adrenergic beta-Antagonist,Adrenergic beta-Receptor Blockader,Adrenergic beta-Receptor Blockaders,beta-Adrenergic Antagonist,beta-Adrenergic Blocker,beta-Adrenergic Blocking Agent,beta-Adrenergic Blocking Agents,beta-Adrenergic Receptor Blockader,beta-Adrenergic Receptor Blockaders,beta-Adrenoceptor Antagonist,beta-Blockers, Adrenergic,beta-Adrenergic Antagonists,beta-Adrenergic Blockers,beta-Adrenoceptor Antagonists,Adrenergic beta Antagonist,Adrenergic beta Antagonists,Adrenergic beta Receptor Blockader,Adrenergic beta Receptor Blockaders,Adrenergic beta-Blockers,Agent, beta-Adrenergic Blocking,Agents, beta-Adrenergic Blocking,Antagonist, beta-Adrenergic,Antagonist, beta-Adrenoceptor,Antagonists, beta-Adrenergic,Antagonists, beta-Adrenoceptor,Blockader, Adrenergic beta-Receptor,Blockader, beta-Adrenergic Receptor,Blockaders, Adrenergic beta-Receptor,Blockaders, beta-Adrenergic Receptor,Blocker, beta-Adrenergic,Blockers, beta-Adrenergic,Blocking Agent, beta-Adrenergic,Blocking Agents, beta-Adrenergic,Receptor Blockader, beta-Adrenergic,Receptor Blockaders, beta-Adrenergic,beta Adrenergic Antagonist,beta Adrenergic Antagonists,beta Adrenergic Blocker,beta Adrenergic Blockers,beta Adrenergic Blocking Agent,beta Adrenergic Blocking Agents,beta Adrenergic Receptor Blockader,beta Adrenergic Receptor Blockaders,beta Adrenoceptor Antagonist,beta Adrenoceptor Antagonists,beta Blockers, Adrenergic,beta-Antagonist, Adrenergic,beta-Antagonists, Adrenergic,beta-Receptor Blockader, Adrenergic,beta-Receptor Blockaders, Adrenergic
D013268	Stimulation, Chemical	The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.	Chemical Stimulation,Chemical Stimulations,Stimulations, Chemical