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Regulation of Cyclic AMP Formation in Cultures of Human Foetal Astrocytes by β 2 ‐Adrenergic and Adenosine Receptors
Author(s) -
Woods Mary D.,
Freshney R.,
Ball Stephen G.,
Vaughan Peter F. T.
Publication year - 1989
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.1471-4159.1989.tb11784.x
Subject(s) - adenosine , isoprenaline , endocrinology , medicine , adenosine receptor , practolol , receptor , adenosine a1 receptor , stimulation , forskolin , cyclase , chemistry , adenylate kinase , biology , agonist , propranolol
Two cell cultures, NEP 2 and NEM 2 , 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 β 2 ‐adrenergic receptors. This study reports that the β 2 ‐adrenergic‐selective antagonist ICI 118,551 is ˜ 1,000 times more potent at inhibiting isoprenaline stimulation of cyclic AMP (cAMP) formation in both NEP 2 and NEM 2 than the β 1 adrenergic‐selective antagonist practolol. This observation confirms the presence of β 2 ‐adrenergic receptors in these cell cultures. The formation of cAMP in NEP 2 is also stimulated by 5′‐( N ‐ethylcarboxamido)adenosine (NECA) more potently than by either adenosine or N 6 ‐(L‐phenylisopropyl)adenosine (L‐PIA), which suggests that this foetal astrocyte expresses adenosine A 2 receptors. Further more, L‐PIA and NECA inhibit isoprenaline stimulation of cAMP formation, a result suggesting the presence of adenosine A 1 receptors on NEP 2 . The presence of A 1 receptors is confirmed by the observation that the A 1 ‐selective antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine reverses the inhibition of isoprenaline stimulation of cAMP formation by L‐PIA and NECA. Additional evidence that NEP 2 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.