A re-investigation of questionable subclassifications of presynaptic α2-autoreceptors: rat vena cava, rat atria, human kidney and guinea-pig urethra

It has been suggested that at least the majority of mammalian presynaptic α2-autoreceptors belong to the genetic α2A/D-adrenoceptor subtype. The aim of the present study was to re-examine the α2-autoreceptors in tissues in which previous assignments conflicted with this α2A/D rule: in the rat vena cava and rat heart atria, where the autoreceptors were classified as α2B or similar to, but not identical with, α2D, and in the human kidney, where they were classified as α2C. Also re-examined were the autoreceptors in the guinea-pig urethra, where they were suggested to be α2A, in agreement with the rule, but in contrast to indications that the α2A/D-adrenoceptor of the guinea pig possesses α2D pharmacological properties. Tissue pieces were preincubated with 3H-noradrenaline and then superfused and stimulated electrically under autoinhibition-free or almost autoinhibition-free conditions. The K d values of up to 14 antagonists (including the partial agonist oxymetazoline) against the release-inhibiting effect of the α2 agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) were determined.