Adrenergic receptors coupled to adenylate cyclase in human cerebromicrovascular endothelium

Abstract

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 beta 1 and beta 2 receptors (propranolol, atenolol, and butoxamine) and for alpha 1-receptors (prazosin) dose-dependently blocked cAMP formation induced by the tested adrenergic agonists. Clonidine, an alpha 2 > alpha 1-agonist, also inhibited isoproterenol-stimulated production of cAMP while yohimbine (alpha 2 > alpha 1 antagonist) augmented the norepinephrine or epinephrine-induced accumulation of cAMP. Cholera toxin-induced ADP ribosylation of the stimulatory guanine nucleotide binding protein (Gs) abolished the stimulatory effect of norepinephrine, epinephrine, phenylephrine or 6-fluoronorepinephrine on cAMP formation. ADP ribosylation of the inhibitory guanine nucleotide binding protein (Gi) 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 beta 1-, beta 2-, alpha 1 and alpha 2-adrenergic receptors linked to adenylate cyclase in endothelium derived from human brain microvasculature. These data also indicate that activation of endothelial alpha 1 -adrenergic receptors is mediated by a signal transduction mechanism associated with Gs protein. The results strongly support the presence of various receptor-controlled adrenergic regulatory mechanisms on human cerebromicrovascular endothelium.

Repetitive hypoglycaemia increases serum adrenaline and induces monocyte adhesion to the endothelium in rat thoracic aorta

“…Adrenaline receptor is a well-known G s proteincoupled receptor, thus the activation of adrenaline receptor results in increased cAMP concentration in endothelial cells [26]. Although several studies have investigated the role of cAMP in the modulation of adhesion molecule abundance, the findings obtained so far remain controversial.…”

Epinephrine Regulation of the Endothelial Nitric-oxide Synthase

“…The S1P response is modulated by S1P 1 receptors that are coupled to G i (36,37), whereas ␤ 3 -adrenergic receptors are coupled to G s pathways (38). It thus appears that the small G protein Rac1 may be a downstream effector of both G s -as well as G i -coupled receptors.…”

Pericapillary and distant axon terminals in the nuclei of the cat amygdala: a morphometric study

“…Our previous studies on the cerebral cortex (Lukaszyk et al 1984), subfornical organ (Wrzolkowa and Lukaszyk 1986) and amygdaloid body (Lukaszyk and Wrzotkowa 1987), together with the observations of other investigators (Raichle et al 1975;Rennels and Nelson 1975;Itakura et al 1977;Swanson et al 1977;Edvinsson et al 1980;Madison et al 1981;Betz and Goldstein 1984;Lou et al 1987;Palmer 1986;Harik 1988;Bacic et al 1992), suggested the existence of a functional connection between axon terminals and capillary vessel walls in the CNS. The results of the present study further support this hypothesis by showing ultrastructural differences between the populations of PAT and DAT in the Cat amygdala.…”