The adenosine receptor-mediated inhibition of noradrenaline release possibly involves an N-protein and is increased by alpha 2-autoreceptor blockade.
The stimulation-evoked overflow of [3H]-noradrenaline from slices of the rabbit hippocampus is inhibited by alpha 2-autoreceptors as well as by adenosine (A1)-receptors. Slices of rabbit hippocampus were labelled with [3H]-noradrenaline, superfused continuously and stimulated twice electrically (rectangular pulses; 2 ms, 3 Hz, 24 mA, 5 V cm-1). Treatment of hippocampal slices with N-ethylmaleimide (NEM, 30 microM; 30 min), which functionally disturbs certain N-proteins, decreased the inhibitory action of adenosine receptor agonists like (-)-N6-(R-phenylisopropyl)-adenosine ((-)-PIA) and adenosine on noradrenaline release. Release inhibition caused by (-)-PIA (0.03-1 microM) was antagonized by NEM in a non-competitive manner in the absence and in the presence of the alpha 2-adrenoceptor antagonist yohimbine. The adenosine receptor antagonist 8-phenyltheophylline significantly increased the evoked noradrenaline release by about 15% in control slices by diminishing the inhibitory action of endogenous adenosine. In NEM-treated slices this effect of 8-phenyltheophylline was not seen. In the presence of (-)-PIA (0.1 microM), i.e. under conditions of an increased inhibitory tone, release facilitation by 8-phenyltheophylline was decreased by NEM compared to that in the respective controls. Occupation of the A1-receptor with (-)-PIA prior to and during the NEM treatment did not protect the A1-receptor-coupled signal transduction system from being affected by NEM. In the presence of the alpha 2-adrenoceptor antagonist yohimbine, the inhibitory action of (-)-PIA was strongly increased. The above results suggest the involvement of a regulatory N-protein in the A1-receptor-mediated inhibition of noradrenaline release and an interaction between the alpha 2-autoreceptor and the A1-receptor-coupled signal transduction system, possibly at the level of a N-protein.
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D005033:Ethylmaleimide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000378:metabolism*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011817:Rabbits; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D011983:Receptors, Purinergic; D010660:Phenylisopropyladenosine; D015016:Yohimbine; D013806:Theophylline; C028322:8-phenyltheophylline; D019204:GTP-Binding Proteins; D000241:Adenosine; D005033:Ethylmaleimide; D009638:Norepinephrine