Investigation of alpha 2-adrenoceptors in humans.

Partial alpha 2-agonists are thought to lower blood pressure principally by stimulation of postsynaptic central nervous system alpha 2-adrenoceptors. It is possible for some to have also a peripheral action, either by acting on the inhibitory presynaptic or as an antagonist at the postsynaptic alpha 2-adrenoceptor. In order to assess these other actions, indices are required for these receptors. Plasma growth hormone is used for the central nervous system and skin blood flow for peripheral postsynaptic alpha 2-adrenoceptors. Plasma insulin is also an index for the latter, but a double-site assay is required to detect decreases within the fasting range. Plasma noradrenaline reflects both central nervous system and peripheral modulation of sympathetic nerve activity, so that "dynamic" tests (described next) are required to dissect these two control mechanisms. Selective peripheral alpha 2-adrenoceptor stimulation or blockade may be attractive for various therapeutic applications such as hypertension, diabetes, and Raynaud's phenomenon. The balance of opposing pre- and postsynaptic alpha 2-adrenoceptor effects will be important and this may require more dynamic tests than already mentioned, such as comparing the effect of alpha-methylnoradrenaline on plasma noradrenaline (presynaptic effect) and skin blood flow (postsynaptic effect) in the presence and absence of the partial alpha 2-agonist or antagonist under investigation. Since alpha-methylnoradrenaline does not penetrate the central nervous system, any blockade of its action by a drug must be peripherally mediated. Examples of all these indices, investigations, and drugs are presented.