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Dopaminergic Receptors Linked to Adenylate Cyclase in Human Cerebromicrovascular Endothelium
Author(s) -
Bacic Fatima,
Uematsu Sumio,
McCarron Richard M.,
Spatz Maria
Publication year - 1991
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.1471-4159.1991.tb06380.x
Subject(s) - ketanserin , medicine , endocrinology , receptor , agonist , cyclase , cholera toxin , chemistry , adenylate kinase , biology , 5 ht receptor , serotonin
: Cultured endothelium derived from three fractions of human cerebral microvessels was used to characterize dopamine (DA) receptors linked to adenylate cyclase activity. DA or D 1 agonist, (±)‐SKF‐82958 hydrobromide, stimulated endothelial cyclic AMP formation in a dose‐dependent manner. The selective D, antagonist, (±)SCH‐23390, inhibited in a dose‐dependent manner the production of cyclic AMP induced by DA. The affinity for the D 1 receptor appeared to be greater in endothelium derived from large and small microvessels than from capillaries. Cholera toxin ADP‐ribosylation of G s proteins abolished the DA stimulatory effect on endothelial adenylate cyclase, whereas pertussis toxin ADP‐ribosylation enhanced the DA‐inducible formation, indicating the presence of both D 1 and D 2 receptors. Agonists of α 1 ‐adrenergic receptors (phenylephrine, 6‐fluoronorepinephrine) or serotonin (5‐HT), which stimulated the production of cyclic AMP, had no additive effect on DA‐stimulated cyclic AMP formation. Incubation of these agents with DA produced the same or lower levels of cyclic AMP as compared to that formed by DA alone. The effect of α 1 ‐adrenergic agonists or 5‐HT on DA production of cyclic AMP was partially prevented by the D 2 antagonist, S (‐)‐sulpiride, or ketanserin (5‐HT 2 > α 1 > H 1 antagonists), respectively. These findings represent the first demonstration of D 1 ‐(stimulatory) and D 2 ‐(inhibitory) receptors linked to adenylate cyclase in microvascular endothelium derived from human brain. The data also indicate that dopaminergic receptors can interact with either α 1 adrenergic or 5‐HT receptors in endothelium on the adenylate cyclase level. These results provide strong support for the previously contemplated existence of a central dopaminergic mechanism in cerebral vessels, a notion that is clinically important.