Article date: February 1995
By: R. Testa, L. Guarneri, E. Poggesi, I. Simonazzi, C. Taddei, A. Leonardi, in Volume 114, Issue 4, pages 745-750
The subtypes of α1‐adrenoceptor mediating contractions to exogenous noradrenaline (NA) in rat aorta have been examined in both biochemical and functional studies.
Incubation of rat aortic membranes with the irreversible α1B‐adrenoceptor antagonist, chloroethylclonidine (CEC: 10 μm) did not change the KD of [3H]‐prazosin binding in comparison to untreated membranes, but reduced by 88% the total number of binding sites (Bmax).
Contractions of rat aortic strips to NA after CEC (50 μm for 30 min) incubation followed by repetitive washing, showed a marked shift in the potency of NA and a partial reduction in the maximum response. The residual contractions to NA after CEC incubation were not affected by prazosin (10 nm).
The competitive antagonists prazosin, terazosin, (R)‐YM‐12617, phentolamine, 5‐methylurapidil and spiperone inhibited contractions to NA with estimated pA2 values of 9.85, 8.54, 9.34, 7.71, 7.64 and 8.41, respectively.
The affinity of the same antagonists for the α1A‐ and α1B‐adrenoceptors was evaluated by utilizing membranes from rat hippocampus pretreated with CEC, and rat liver, respectively. 5‐Methylurapidil and phentolamine were confirmed as selective for the α1A‐adrenoceptors, whereas spiperone was α1B‐selective.
A significant correlation was found between the pA2 values of the α1‐adrenoceptor antagonists tested and their affinity for the α1B‐adrenoceptor subtype, but not for the α1A‐subtype.
In conclusion, these findings indicate that in rat aorta most of the contraction is mediated by α1B‐adrenoceptors, and that the potency (pA2) of an antagonist in this tissue should be related to its antagonistic effect on this subtype of the α1‐adrenoceptor population.
The subtypes of α1‐adrenoceptor mediating contractions to exogenous noradrenaline (NA) in rat aorta have been examined in both biochemical and functional studies.
Incubation of rat aortic membranes with the irreversible α1B‐adrenoceptor antagonist, chloroethylclonidine (CEC: 10 μm) did not change the KD of [3H]‐prazosin binding in comparison to untreated membranes, but reduced by 88% the total number of binding sites (Bmax).
Contractions of rat aortic strips to NA after CEC (50 μm for 30 min) incubation followed by repetitive washing, showed a marked shift in the potency of NA and a partial reduction in the maximum response. The residual contractions to NA after CEC incubation were not affected by prazosin (10 nm).
The competitive antagonists prazosin, terazosin, (R)‐YM‐12617, phentolamine, 5‐methylurapidil and spiperone inhibited contractions to NA with estimated pA2 values of 9.85, 8.54, 9.34, 7.71, 7.64 and 8.41, respectively.
The affinity of the same antagonists for the α1A‐ and α1B‐adrenoceptors was evaluated by utilizing membranes from rat hippocampus pretreated with CEC, and rat liver, respectively. 5‐Methylurapidil and phentolamine were confirmed as selective for the α1A‐adrenoceptors, whereas spiperone was α1B‐selective.
A significant correlation was found between the pA2 values of the α1‐adrenoceptor antagonists tested and their affinity for the α1B‐adrenoceptor subtype, but not for the α1A‐subtype.
In conclusion, these findings indicate that in rat aorta most of the contraction is mediated by α1B‐adrenoceptors, and that the potency (pA2) of an antagonist in this tissue should be related to its antagonistic effect on this subtype of the α1‐adrenoceptor population.
DOI: 10.1111/j.1476-5381.1995.tb13267.x
View this article