Regulation of Cyclic AMP Formation in Cultures of Human Foetal Astrocytes by β2‐Adrenergic and Adenosine Receptors

Publisher Website
Google Scholar
Abstract
Two cell cultures, NEP2 and NEM2, isolated from human foetal brain have been maintained through several passages and found to express some properties of astrocytes. Both cell cultures contain adenylate cyclase stimulated by catecholamines with a potency order of isoprenaline > adrenaline > salbutamol < noradrenaline, which is consistent with the presence of β2-adrenergic receptors. This study reports that the β2-adrenergic-selective antagonist ICI 118,551 is ˜ 1,000 times more potent at inhibiting isoprenaline stimulation of cyclic AMP (cAMP) formation in both NEP2 and NEM2 than the β1adrenergic-selective antagonist practolol. This observation confirms the presence of β2-adrenergic receptors in these cell cultures. The formation of cAMP in NEP2 is also stimulated by 5′-(N-ethylcarboxamido)adenosine (NECA) more potently than by either adenosine or N6-(L-phenylisopropyl)adenosine (L-PIA), which suggests that this foetal astrocyte expresses adenosine A2 receptors. Further more, L-PIA and NECA inhibit isoprenaline stimulation of cAMP formation, a result suggesting the presence of adenosine A1 receptors on NEP2. The presence of A1 receptors is confirmed by the observation that the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine reverses the inhibition of isoprenaline stimulation of cAMP formation by L-PIA and NECA. Additional evidence that NEP2 expresses adenosine receptors linked to the adenylate cyclase-inhibitory GTP-binding protein is provided by the finding that pretreatment of these cells with pertussis toxin reverses the adenosine inhibition of cAMP formation stimulated by either isoprenaline or forskolin.