Mediation of noradrenaline‐induced contractions of rat aorta by the (α_1B‐adrenoceptor subtype

Abstract

1. The subtypes of alpha 1-adrenoceptor mediating contractions to exogenous noradrenaline (NA) in rat aorta have been examined in both biochemical and functional studies. 2. Incubation of rat aortic membranes with the irreversible alpha 1B-adrenoceptor antagonist, chloroethylclonidine (CEC: 10 microM) 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). 3. Contractions of rat aortic strips to NA after CEC (50 microM 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). 4. 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. 5. The affinity of the same antagonists for the alpha 1A- and alpha 1B- 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 alpha 1A-adrenoceptors, whereas spiperone was alpha 1B-selective. 6. A significant correlation was found between the pA2 values of the alpha 1-adrenoceptor antagonists tested and their affinity for the alpha 1B-adrenoceptor subtype, but not for the alpha 1A-subtype. 7. In conclusion, these findings indicate that in rat aorta most of the contraction is mediated by alpha 1B-adrenoceptors, and that the potency (pA2) of an antagonist in this tissue should be related to its antagonistic effect on this subtype of the alpha 1-adrenoceptor population.

Affinity of Serotonin Receptor Antagonists and Agonists to Recombinant and Native α1-Adrenoceptor Subtypes

“…High affinity of spiperone to a1b-adrenoceptors has been demonstrated in binding studies (10,28). Such a1b-selectivity was detected in the present binding experiment but the functional data did not support the selectivity.…”

A possible structural determinant of selectivity of boldine and derivatives for the α1A‐adrenoceptor subtype

“…To date, the data on the a,-adrenoceptor subtypes present in rat aorta are confusing. Although some studies have suggested that the al-adrenoceptor population is a homogeneous entity which has been postulated to be either aIA (Beckering & Brodde, 1989), a1B (Eltze & Boer, 1992;Testa et al, 1995), non-calA/non-oxlB (Oriowo & Ruffolo, 1992;Aboud et al, 1993), ,ID (Ko et al, 1994), or 'predominantly' 21D , others have suggested that a number of different subtypes contribute to the contractile response in rat aorta ; Van der Graaf et al, 1996). Moreover, Rokosh et al (1994) andPiascik et al (1994) reported that they could detect mRNA for the alb, al, and dLd adrenoceptors in the rat aorta.…”

Effect of Glucagon-Like Peptide-1(7–36) and Exendin-4 on the Vascular Reactivity in Streptozotocin/Nicotinamide-Induced Diabetic Rats

“…The contractile response induced by NA was biphasic and is mediated through both ␣ 1 -and ␣ 2 -adrenoceptors [43,44] , but ␣ 1 -adrenoceptor is thought to play the predominant role in mediating NA-stimulated contraction. Actually, it has been suggested that in rat aorta most of the NA-induced contraction is especially mediated by the ␣ 1B [47] and ␣ 1D [48] receptor subtypes, and in the high insulintreated diabetic aorta the expressions of the mRNA for the ␣ 1B and ␣ 1D adrenoceptor were both signifi cantly greater than in the untreated control [49] . An insulin-releasing effect of GLP-1 may also contribute to its beneficial effect on the vascular system.…”