ISSN:
1432-1912
Keywords:
Key wordsα2-Adrenoceptor subtypes
;
α2-Autoreceptors
;
α2A-Adrenoceptor
;
α2D-Adrenoceptor
;
Rat vena cava
;
Rat atria
;
Human
;
kidney
;
Guinea-pig urethra
;
Noradrenaline release
;
Oxymetazoline
;
UK 14
;
304
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Description / Table of Contents:
EC 50 between 6.3 and 13.2 nM. All antagonists (except prazosin in one case) shifted the concentration-inhibition curve of UK 14,304 to the right. Comparison of the K d values thus obtained with K d values at known α2 subtypes indicated that the autoreceptors in the rat vena cava, rat atria and the guinea-pig urethra were α2D and those in the human kidney α2A. For example, the pK d values of the antagonists in the rat vena cava, in rat atria and in the guinea-pig urethra were closely correlated with pK d values at the prototypic α2D radioligand binding sites in the bovine pineal gland (r = 0.96, P 〈 0.001; r = 0.92, P 〈 0.01; and r = 0.95; P 〈 0.001) and with the pK d values at the α2D-autoreceptors of guinea-pig atria (r = 0.99, P 〈 0.001; r = 0.95, P 〈 0.001; and r = 0.98, P 〈 0.001). The pK d values at the autoreceptors in rat vena cava, rat atria and guinea-pig urethra were not significantly or more loosely correlated with pK d values at α2A, α2B and α2C binding sites and α2A-autoreceptors. On the other hand, the pK d values of the antagonists in the human kidney were closely correlated with pK d values at the prototypic α2A radioligand binding sites in HT29 cells (r = 0.95; P 〈 0.001) and with pK d values at the α2A-autoreceptors of the pig brain cortex (r = 0.97; P 〈 0.001), but were not significantly or more loosely correlated with pK d values at α2B, α2C and α2D binding sites and α2D-autoreceptors.
Abstract:
2D , those in the human kidney α2A, and those in the guinea-pig urethra equally α2D. All, therefore, conform to the rule that α2-autoreceptors belong at least predominantly to the genetic α2A/D subtype of the α2-adrenoceptor. The apparent paradox of an α2A-autoreceptor in the urethra of the guinea pig, a species in which the genetic α2A/D-adrenoceptor otherwise has α2D pharmacological properties, is removed.
Notes:
Abstract 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/PL00005111
