Biomaterial Database

Receptor (norepinephrine), P-site (2',5'-dideoxyadenosine), and calcium-mediated inhibition of prostaglandin and forskolin-activated cyclic AMP-generating systems in human platelets. 1985

A M Siegl, and J W Daly

Prostaglandin D2, 2-chloroadenosine, forskolin and combinations of these agents increase cyclic AMP-levels in intact human platelets. The inhibition of activated cyclic AMP-generating systems by 1) alpha2-adrenergic receptor-mediated hormonal input (norepinephrine), 2) a P-site agent (2',5'-dideoxyadenosine) and 3) a divalent cation (calcium) were examined: 1) Norepinephrine produces non-competitive inhibition of both forskolin and prostaglandin D2(PGD2)-stimulated cyclic AMP-accumulation in intact human platelets. The Ki values for norepinephrine versus forskolin, PGD2 and 2-chloroadenosine are similar in magnitude, while the Ki versus a forskolin-PGD2 combination is approximately 10-fold greater. Onset of inhibition by norepinephrine of the PGD2-response is several fold faster than for the forskolin-response. When platelets stimulated by the forskolin and PGD2 combination are exposed to norepinephrine, there is a transient increase in levels of cyclic AMP due to the potentiation of a minor beta-adrenergic component. This stimulation is followed by inhibition. 2) 2',5'-Dideoxyadenosine produces a non-competitive inhibition of the forskolin-response with a Ki of 110 microM. The inhibition of the PGD2-response by 2',5'-dideoxyadenosine is competitive with a Ki of 6-13 microM, while inhibition of the forskolin-PGD2 response has a Ki of 30 microM. Onset of inhibition by 2',5'-dideoxyadenosine is identical for forskolin or PGD2-stimulated platelets. There is a lag period for inhibition of platelets stimulated with the forskolin-PGD2 combination. The PGD2-forskolin combination appears to stabilize the cyclic AMP-generating system of platelets against inhibition by either norepinephrine or 2',5'-dideoxyadenosine. 3) Calcium ions cause a similar inhibition of cyclic AMP-generation in intact platelets, regardless of the type of stimulation.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
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
D011448	Prostaglandin Antagonists	Compounds that inhibit the action of prostaglandins.	Prostaglandin Inhibitors,Antagonists, Prostaglandin,Inhibitors, Prostaglandin,Prostaglandin Antagonist,Prostaglandin Inhibitor,Antagonist, Prostaglandin,Inhibitor, Prostaglandin
D011457	Prostaglandins D	Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects.	PGD
D011941	Receptors, Adrenergic	Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction.	Adrenergic Receptors,Adrenoceptor,Adrenoceptors,Norepinephrine Receptor,Receptors, Epinephrine,Receptors, Norepinephrine,Adrenergic Receptor,Epinephrine Receptors,Norepinephrine Receptors,Receptor, Adrenergic,Receptor, Norepinephrine
D001792	Blood Platelets	Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.	Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D003839	Deoxyadenosines	Adenosine molecules which can be substituted in any position, but are lacking one hydroxyl group in the ribose part of the molecule.	Adenine Deoxyribonucleosides,Adenylyldeoxyribonucleosides,Deoxyadenosine Derivatives,Deoxyribonucleosides, Adenine,Derivatives, Deoxyadenosine
D004224	Diterpenes	Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate.	Diterpene,Diterpenes, Cembrane,Diterpenes, Labdane,Diterpenoid,Labdane Diterpene,Norditerpene,Norditerpenes,Norditerpenoid,Cembranes,Diterpenoids,Labdanes,Norditerpenoids,Cembrane Diterpenes,Diterpene, Labdane,Labdane Diterpenes
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