van Tits L J, Daul A, Grosse-Wilde H, Brodde O E
Biochemical Research Laboratories, University of Essen, FRG.
Br J Clin Pharmacol. 1990;30 Suppl 1(Suppl 1):148S-149S. doi: 10.1111/j.1365-2125.1990.tb05489.x.
The effect of intracellular increases of cyclic adenosine monophosphate (cAMP) on the accumulation of inositol phosphates (IPs) in response to various mitogens in vitro in human peripheral mononuclear leucocytes (MNL) was investigated. The beta-adrenoceptor agonists inhibited mitogen-induced IPs-accumulation by about 30-50% with a rank order of potency isoprenaline greater than adrenaline much greater than noradrenaline. This rank order corresponded with the order of potency of the beta-adrenoceptor agonists to generate cAMP. The beta-adrenoceptor agonist-induced inhibition of IPs-accumulation in response to mitogen could be completely prevented by the beta 2-adrenoceptor selective antagonist ICI 118,551, but not by the beta 1-adrenoceptor selective antagonist CGP 20712A. Furthermore, the isoprenaline-induced inhibition of IPs-accumulation in response to mitogen could be enhanced by the phosphodiesterase inhibitor IBMX. We conclude that cAMP antagonizes mitogen-induced IPs-accumulation in human peripheral MNL in vitro.
研究了细胞内环磷酸腺苷(cAMP)增加对人外周血单个核白细胞(MNL)体外对各种有丝分裂原反应时肌醇磷酸(IPs)积累的影响。β-肾上腺素能受体激动剂抑制有丝分裂原诱导的IPs积累约30%-50%,其效力顺序为异丙肾上腺素大于肾上腺素远大于去甲肾上腺素。该顺序与β-肾上腺素能受体激动剂产生cAMP的效力顺序一致。β-肾上腺素能受体激动剂诱导的对有丝分裂原的IPs积累抑制可被β2-肾上腺素能受体选择性拮抗剂ICI 118,551完全阻断,但不能被β1-肾上腺素能受体选择性拮抗剂CGP 20712A阻断。此外,磷酸二酯酶抑制剂异丁基甲基黄嘌呤(IBMX)可增强异丙肾上腺素诱导的对有丝分裂原的IPs积累抑制。我们得出结论,cAMP在体外拮抗人外周血MNL中有丝分裂原诱导的IPs积累。