ADRENERGIC-RECEPTORS COUPLED TO ADENYLATE-CYCLASE IN HUMAN CEREBROMICROVASCULAR ENDOTHELIUM

被引:24
作者
BACIC, F
MCCARRON, RM
UEMATSU, S
SPATZ, M
机构
[1] NINCDS,STROKE BRANCH,BLDG 36,ROOM 4B22,BETHESDA,MD 20892
[2] JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205
关键词
ADRENERGIC RECEPTORS; CAMP; CEREBROVASCULAR ENDOTHELIUM; ADENYLATE CYSLASE;
D O I
10.1007/BF01000158
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cultured endothelium derived from three microvascular fractions of human brain was used to characterize adrenergic receptors coupled to adenylate cyclase activity. Catecholamines (norepinephrine, epinephrine) and their analogs (isoproterenol, phenylephrine, 6-fluoronorepinephrine) dose-dependently stimulated endothelial production of cAMP. Antagonists for beta1 and beta2 receptors (propranolol, atenolol, and butoxamine) and for alpha1 receptors (prazosin) dose-dependently blocked cAMP formation induced by the tested adrenergic agonists. Clonidine, an alpha2>alpha1-agonist, also inhibited isoproterenol-stimulated production of cAMP while yohimbine (alpha2>alpha1 antagonist) augmented the norepinephrine or epinephrine-induced accumulation of cAMP. Cholera toxin-induced ADP ribosylation of the stimulatory guanine nucleotide binding protein (G(s)) abolished the stimulatory effect of norepinephrine, epinephrine, phenylephrine or 6-fluoronorepinephrine on cAMP formation. ADP ribosylation of the inhibitory guanine nucleotide binding protein (G(i) by pertussis toxin had no effect on either phenylephrine- or 6-fluoronorepinephrine-induced production of cAMP while it increased the norepinephrine and epinephrine-induced accumulation of cAMP. These findings represent the first documentation of beta1-, beta2-, alpha2 and alpha2-adrenergic receptors linked to adenylate cyclase in endothelium derived from human brain microvasculature. These data also indicate that activation of endothelial alpha1-adrenergic receptors is mediated by a signal transduction mechanism associated with G(s) protein. The results strongly support the presence of various receptor-controlled adrenergic regulatory mechanisms on human cerebromicrovascular endothelium.
引用
收藏
页码:125 / 137
页数:13
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