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Catecholamine‐Sensitive Guanylate Cyclase from Human Caudate Nucleus
Author(s) -
Frey William H.,
Senogles Susan E.,
Heston Leonard L.,
Tuason Vicente B.,
Nicol Susan E.
Publication year - 1980
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1980.tb09018.x
Subject(s) - dithiothreitol , chemistry , gucy1a3 , gucy1b3 , dopamine , biochemistry , adrenochrome , nomifensine , cyclase , enzyme , guanylate cyclase 2c , epinephrine , dopaminergic , endocrinology , biology
Partial purification of soluble guanylate cyclase on DEAE‐Sephacel yields two separate peaks of guanylate cyclase activity. After 10‐fold purification of the soluble enzyme, guanylate cyclase is markedly inhibited by micromolar concentrations of dopamine (I 50 = 0.2 μm). Dopamine inhibition is observed whether the reaction is conducted with Mn 21 or with Mg 2+ , under atmosphere or N 2 (g), and using enzyme from either peak from the DEAESephacel column. Other catecholamines also inhibit partially purified guanylate cyclase with an order of potency at 1 μ m of: dopamine = l ‐DOPA > norepinephrine = isoproterenol = adrenochrome > epinephrine. The structural requirements for inhibition are two free hydroxyl groups on the phenyl ring and an ethylamine side chain. Dopamine also inhibits the Triton X‐100‐solubilized microsomal guanylate cyclase after partial purification on DEAESephacel. Neither chlorpromazine, propranolol, nor phentolamine at 20 μ m effectively block the dopamine inhibition of partially purified soluble guanylate cyclase. Micromolar concentrations of the reducing agents dithiothreitol and glutathione also inhibit partially purified guanylate cyclase, but unlike these agents, catecholamines can inhibit whether added in the reduced or the oxidized forms. Inhibition of enzyme activity by micromolar concentrations of dopamine, adrenochrome, or dithiothreitol is rapidly reversed by dilution and the dopamine inhibition is competitive with MgGTP. Inhibition does not appear to involve covalent binding or to result from the ability of catecholamines to reduce the concentrations of oxygen or free radicals in solution.