Baba A, Nishiuchi Y, Uemura A, Iwata H
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
J Pharmacol Exp Ther. 1988 Apr;245(1):299-304.
We show the involvement of chloride transport on excitatory amino acids-induced accumulation of cyclic AMP in brain slices. The stimulation of cyclic AMP formation induced by excitatory amino acids in guinea pig hippocampal slices was absolutely dependent on the presence of Cl- in the incubation medium. The apparent half-maximal concentration of chloride was about 30 to 40 mM with the maximum response at more than 60 mM. As regards to the anion selectivity for the stimulation by excitatory amino acids, Br- was fully effective as Cl-, whereas F- and SO42- were ineffective. DL-(+/-)-2-Amino-4-phosphonobutyric acid, an antagonist of excitatory amino acid receptors, reduced significantly the response to excitatory amino acids. In the Cl- -free medium, the stimulatory effects of 50 microM veratridine, 10 microM forskolin and 100 microM histamine were reduced markedly but still significantly observed. The anion exchange blockers at the concentrations of more than 1 mM reduced significantly the cyclic AMP formation induced by an excitatory amino acid in a dose-dependent manner. Furosemide at the concentration of 3 mM negated the Cl- -dependent responses to forskolin and histamine without affecting the Cl- -independent ones. Furosemide did not inhibit the adenylate cyclase activity of hippocampal synaptic membrane fractions.
我们展示了氯化物转运在兴奋性氨基酸诱导的脑片环磷酸腺苷（cAMP）积累中的作用。兴奋性氨基酸在豚鼠海马脑片中诱导的cAMP形成刺激绝对依赖于孵育介质中Cl-的存在。氯化物的表观半最大浓度约为30至40 mM，在超过60 mM时出现最大反应。关于兴奋性氨基酸刺激的阴离子选择性，Br-与Cl-一样完全有效，而F-和SO42-则无效。兴奋性氨基酸受体拮抗剂DL-(+/-)-2-氨基-4-膦酸丁酸显著降低了对兴奋性氨基酸的反应。在无Cl-的介质中，50μM藜芦碱、10μM福斯高林和100μM组胺的刺激作用明显降低，但仍有显著观察到。浓度超过1 mM的阴离子交换阻滞剂以剂量依赖的方式显著降低了兴奋性氨基酸诱导的cAMP形成。3 mM浓度的呋塞米消除了对福斯高林和组胺的Cl-依赖性反应，而不影响Cl-非依赖性反应。呋塞米不抑制海马突触膜组分的腺苷酸环化酶活性。
