흰쥐 해마에서 Norepinephrine 유리에 미치는 N6-cyclopentyladenosine 및 Forskolin의 영향

Interaction of Forskolin with the Effect of N6-cyclopentyladenosine on Norepinephrine Release in Rat Hippocampus

<P> As it has been reported that the depolarization-induced norepinephrine (NE) release is modulated by activation of presynaptic A<SUB>1</SUB>-adenosine heteroreceptor and various lines of evidence indicate the involvement of adenylate cyclase system in A<SUB>1</SUB>-adenosine post-receptor mechanism in hippocampus, it was attempted to delineate the role of adenylate cyclase system in the A<SUB>1</SUB>-receptor-mediated control of NE release in this study. Slices from rat hippocampus were equilibrated with [<SUP>3</SUP>H]-NE and the release of the labelled products was evoked by electrical stimulation (3 Hz, 5 Vcm<SUP>-1</SUP>, 2 ms, rectangular pulses). The influence of various agents on the evoked tritium-outflow was investigated. <P> N<SUP>6</SUP>-Cyclopentyladenosine (CPA), a specific A<SUB>1</SUB>-adenosine receptor agonist, in concentrations ranging from 0.1 to 10 &#12557;M decreased the [<SUP>3</SUP>H]-NE release in a dose-dependent manner without any change of basal rate of release. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX, 2 &#12557;M), a selective A<SUB>1</SUB>-receptor antagonist, inhibited the CPA effect. The responses to N-ethylmaleimide (3 &amp; 10 &#12557;M), a SH-alkylating agent of G-protein, were characterized by increments of the evoked NE-release and the CPA effects were completely abolished by NEM pretreatment. Forskolin, a specific adenylate cyclase activator, in concentrations ranging from 0.1 to 30 &#12557;M increased the evoked and basal rate of NE release in a dose-dependent manner and the CPA effects were inhibited by forskolin pretreatment. Rolipram (1 &amp; 10 &#12557;M), a phosphodiesterase inhibitor, did not affect the evoked NE release, but reduced the CPA effect. And 8-bromo-cAMP (100 &amp; 300 &#12557;M), a membrane permeable cAMP analogue, inhibited the CPA effect significantly. <P> These results suggest that the A<SUB>1</SUB>-adenosine heteroreceptor plays an important role in NE-release via nucleotide- binding protein G<SUB>i</SUB> in the rat hippocampus and that the adenylate cyclase system might be participated in this process.