Is forskolin stimulation of rat striatal tyrosine hydroxylase dependent on adenylate cyclase activation? 1992

P Onali, and M C Olianas
Department of Neurosciences, University of Cagliari, Italy.

Because some responses to forskolin are adenosine 3',5'-cyclic phosphate (cyclic AMP) independent, we investigated the involvement of adenylate cyclase in the stimulatory effect of forskolin on synaptosomal tyrosine hydroxylase (TH) activity of rat striatum. The forskolin analogue, 1,9-dideoxyforskolin, which mimics the cyclic AMP-independent effects of forskolin, was a very weak activator of both striatal adenylate cyclase and tyrosine hydroxylase activities, whereas forskolin stimulated the two enzymes effectively and with similar potencies. Moreover, exposure of synaptosomes to the specific cyclic AMP antagonist Rp-adenosine 3',5'-cyclic phosphorothioate reduced basal TH activity and counteracted the stimulatory effect on the enzyme activity by submaximal concentrations of forskolin. These results provide circumstantial evidence that in striatal dopaminergic nerve terminals a presynaptic adenylate cyclase mediates the stimulation of TH activity by forskolin.

UI MeSH Term Description Entries
D008297 Male Males
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
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
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
D000262 Adenylyl Cyclases Enzymes of the lyase class that catalyze the formation of CYCLIC AMP and pyrophosphate from ATP. Adenyl Cyclase,Adenylate Cyclase,3',5'-cyclic AMP Synthetase,Adenylyl Cyclase,3',5' cyclic AMP Synthetase,AMP Synthetase, 3',5'-cyclic,Cyclase, Adenyl,Cyclase, Adenylate,Cyclase, Adenylyl,Cyclases, Adenylyl,Synthetase, 3',5'-cyclic AMP
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
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
D013574 Synaptosomes Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. Synaptosome
D013873 Thionucleotides Nucleotides in which the base moiety is substituted with one or more sulfur atoms.

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