Alpha 2-adrenoceptor mediated inhibition of forskolin-stimulated cyclic AMP accumulation in isolated porcine palmar lateral veins. 1995

I K Wright, and D A Kendall, and V G Wilson
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, UK.

The aim of this study was to use a 3H-adenine pre-labelling technique to characterise the effect of alpha 2-adrenoceptor activation on forskolin-stimulated cyclic AMP accumulation in the isolated porcine palmar lateral vein. Forskolin (10(-7)-10(-4) M) stimulated 3H-cyclic AMP accumulation in the isolated porcine palmar lateral vein in a biphasic and concentration-dependent manner. In the absence of the cyclic AMP-selective phosphodiesterase inhibitor rolipram, forskolin stimulated 3H-cyclic AMP accumulation approximately 7-8 fold. The response reached a peak after 5 min. In the presence of rolipram (10(-5) M), basal 3H-cyclic AMP levels were approximately 70% higher than in its absence (basal: 1823 +/- 57 dpm; rolipram: 3088 +/- 229, n = 3) and forskolin (3 x 10(-5) M) stimulated 3H-cyclic AMP accumulation approximately 8 fold. The latter response reached a plateau 10 min after the addition of forskolin. In all subsequent studies, the tissues were incubated with forskolin (3 x 10(-5) M) for 5 min in the absence of rolipram. Noradrenaline (NA; 10(-9)-10(-4) M) and UK14304 (10(-9)-10(-4) M) inhibited forskolin-stimulated 3H-cyclic AMP accumulation in a concentration-dependent manner with mean pIC50 values of 7.61 +/- 0.37 (n = 4) and 7.76 +/- 0.23 (n = 5), respectively. With either NA or UK14304, the maximal inhibition of the forskolin response obtained was approximately 75%. Neither NA (10(-4) M) nor UK14304 (10(-4) M) altered basal 3H-cyclic AMP levels.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D008297 Male Males
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010656 Phenylephrine An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent. (R)-3-Hydroxy-alpha-((methylamino)methyl)benzenemethanol,Metaoxedrin,Metasympatol,Mezaton,Neo-Synephrine,Neosynephrine,Phenylephrine Hydrochloride,Phenylephrine Tannate,Neo Synephrine,Tannate, Phenylephrine
D011224 Prazosin A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION. Furazosin,Minipress,Pratsiol,Prazosin HCL,Prazosin Hydrochloride,HCL, Prazosin,Hydrochloride, Prazosin
D011760 Pyrrolidinones A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed) Pyrrolidinone,Pyrrolidone,Pyrrolidones
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
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
D000225 Adenine A purine base and a fundamental unit of ADENINE NUCLEOTIDES. Vitamin B 4,4, Vitamin B,B 4, Vitamin

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