Effects of N‐ethylmaleimide and forskolin on noradrenaline release from rat hippocampal slices. Evidence that prejunctional adenosine and a‐receptors are linked to A/‐proteins but not to adenylate cyclase

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Abstract
N‐ethylmaleimide (NEM) treatment has been shown to inactivate regulatory GTP‐binding N (G)‐proteins in many preparations, including slices of rat hippocampus. NEM‐treatment (100 μM for 15 min) has been used to examine the possible involvement of a N‐protein in the prejunctional inhibitory effect of an adenosine analogue, R‐PIA acting on A,‐receptors, and of clonidine acting on a,‐adrenoceptors in this tissue. NEM treatment significantly enhanced basal overflow of [3H]NA and the overflow stimulated by low (0.3 Hz) frequency stimulation, but not the overflow stimulated by higher (1–10 Hz) frequency stimulation. The prejunctional inhibitory effect of R‐PIA (I μM) on NA release, stimulated by a 3 Hz stimulation, was abolished by NEM pretreatment, which also eliminated the dosedependent prejunctional effect of clonidine and reduced the facilitatory effect of yohimbine. Forskolin had a small, but significant stimulatory effect on NA overflow, but did not reduce the prejunctional inhibitory effect of R‐PIA. The adenylate cyclase inhibitor SQ22, 536did not reduce NA overflow. These results show that NEM blocks a critical step in the prejunctional action of both adenosine‐and a,‐receptor agonists, which may be a N‐protein. The possibility is discussed that the prejunctional A,‐ and a,‐receptors couple to aN‐protein that controls a different effector than adenylate cyclase.

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