Interactions between the presynaptic alpha2-autoreceptor and presynaptic inhibitory heteroreceptors on noradrenergic neurones.

The noradrenergic neurones of the autonomic nervous system (postganglionic sympathetic neurones) and of the central nervous system are endowed with presynaptic receptors by which noradrenaline release is inhibited by noradrenaline itself (via the alpha2-autoreceptor) and by other transmitters and mediators (via heteroreceptors). Frequently, but not consistently, inhibitory interactions exist between auto- and heteroreceptors. This holds true for the following heteroreceptors: adenosine A1, cannabinoid CB1, dopamine D2/D3, histamine H3, 5-hydroxytryptamine (serotonin) 5-HT(1B), imidazoline, muscarine M2, delta opioid, kappa opioid, mu opioid, orphan opioid (ORL1), prostaglandin EP3, and somatostatin SRIF1. Such interactions (which have also been obtained in human tissue) may, if not considered, prevent the identification of a putative heteroreceptor or the quantitative estimation of the effect mediated by this receptor, and they may explain drug interactions in humans in vivo; many ligands at the alpha2-autoreceptor and at the heteroreceptors may be simultaneously used for therapeutic reasons (e.g., carbachol, clonidine, dopamine, sumatriptan, mianserin, and misoprostol) or abused (e.g., heroin, LSD, and delta9-tetrahydrocannabinol in hashish or marijuana).