BMY 7378 is a selective antagonist of the D subtype of α1-adrenoceptors

Goetz, Aaron S.; King, Holly K.; Ward, Stuart D.C.; True, Timothy A.; Rimele, Thomas J.; Saussy, David L.

doi:10.1016/0014-2999(94)00751-r

Cited by 292 publications

(254 citation statements)

References 5 publications

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“…The affinity of a range of competitive antagonists has now been measured on membranes from cells transfected with the cDNA for each of the three cloned al subtypes in several studies. While prazosin has been found to be non-selective, others have shown some degree of selectivity between the subtypes (Faure et al, 1994;Forray et al, 1994b;Kenny et al, 1994a,b;Testa et al, 1994;Goetz et al, 1995). The affinity of the same antagonists has been measured here in functional studies for the al subtype mediating contraction of the prostate by calculation of pA2 values.…”

Section: Discussionmentioning

confidence: 89%

“…The responses to noradrenaline were not affected by the highest concentration Faure et al, 1994;Forray et al, 1994b;Kenny et al, 1994a,b;Testa et al, 1994;Goetz et al, 1995 (no s.e.mean for compounds with only one or two values). In each study the hamster alb, bovine aln and rat ald clones were used except for Goetz et al (1995) and Forray et al (1994b) where the three human al-subtype clones were used.…”

Section: Resultsmentioning

confidence: 96%

“…The affinity of the same antagonists has been measured here in functional studies for the al subtype mediating contraction of the prostate by calculation of pA2 values. Table 1 compares the pA2 values obtained for these antagonists with their average published pKi values on the expressed cloned subtypes (Faure et al, 1994;Forray et al, 1994b;Kenny et al, 1994a,b;Testa et al, 1994;Goetz et al, 1995). The pA2 values have been plotted against their average pKi values for each of the cloned subtypes in order to see with which one the functional al-adrenoceptor mediating contraction in the human prostate most closely correlates (Figure 10).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Noradrenaline contractions of human prostate mediated by α_1c‐(α_1c‐) adrenoceptor subtype

Marshall

Burt

Chapple

1995

British J Pharmacology

152

111

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1 The subtype of a1-adrenoceptor mediating contractions of human prostate to noradrenaline was characterized by use of a range of competitive and non-competitive antagonists. 2 Contractions of the prostate to either noradrenaline (pD2 5.5), phenylephrine (pD2 5.1) or methoxamine (pD2 4.4) were unaltered by the presence of neuronal and extraneuronal uptake blockers. Noradrenaline was about 3 and 10 times more potent than phenylephrine and methoxamine respectively. Phenylephrine and methoxamine were partial agonists. 3 Pretreatment with the alkylating agent, chlorethylclonidine (10-4 M) shifted the noradrenaline concentration-contraction curve about 3 fold to the right and depressed the maximum response by 31%. This shift is 100 fold less than that previously shown to be produced by chlorethylclonidine under the same conditions on OlB-adrenoceptor-mediated contractions. 4 Cumulative concentration-contraction curves for noradrenaline were competitively antagonized by WB 4101 (pA2 9.0), 5-methyl-urapidil (pA2 8.6), phentolamine (pA2 7.6), benoxathian (pA2 8.

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Section: Discussionmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Noradrenaline contractions of human prostate mediated by α_1c‐(α_1c‐) adrenoceptor subtype

Marshall

Burt

Chapple

1995

British J Pharmacology

152

111

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“…Three subtypes of α1-adrenoceptors have been classified on the basis of pharmacological and molecular biology criteria (MacDougall et al, 2006), and are referred to as α1A, α1B and α1D receptors. BMY7378 is a highly selective antagonist of the α1D-adrenoceptor subtype (Goetz et al, 1995) and can be used to distinguish α1-adrenoceptor subtypes present in different tissues. Studies measuring mRNA have demonstrated that the rat renal artery expresses the α1D-adrenoceptor subtype (Piascik et al, 1994) at a level comparable to that in the aorta (Suzuki et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Characteristics of contractile activity in the renal artery of ovariectomized rats

Enkhjargal

Hashimoto

Kinoshita

et al. 2008

J. Smooth Muscle Res.

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The incidence of cardiovascular disease is markedly lower in cycling, pre-menopausal women and post-menopausal women receiving estrogen than in men or untreated postmenopausal women. Clinical studies demonstrate a protective role of estrogen in hormone replacement therapy in terms of reducing cardiovascular risk. However, the benefits of hormone replacement therapy in cardiovascular disease remain unclear. We investigated the effects of estrogen on the contractile responses of the renal artery of ovariectomized Wistar rats (OVX) compared to both ovariectomized 17β-estradiol-treated rats (OVXE) and sham-operated (control) rats. Isometric contraction of renal artery was recorded with a strain gauge transducer. The maximum contractile response of the renal artery smooth muscle to KCl (80 mM) in the OVXE group was significantly higher than that in both the control and OVX groups. The phenylephrine (PE) concentration-response curves in all three groups indicated a greater sensitivity at lower concentrations of PE following treatment with 100 µM L-arginine methyl ester (L-NAME). The EC50 values for PE in the three groups were 2 times lower in the presence of L-NAME than those lacking exposure to L-NAME. The EC50 value for PE in the OVX group was ~3 times lower in the presence of L-NAME than in those lacking exposure to L-NAME and 100 nM BMY 7378, an α1D-adrenoceptor antagonist. The rate of relaxation of the PE-induced contraction (T1/2) was significantly reduced in the OVX group relative to both the control and OVXE groups.T1/2 values after treatment with 100 µM L-NAME were slower than those lacking exposure to L-NAME in all groups. Further, the T1/2 value of the OVX group was 2 times greater than that of the control; this change was reversed in the OVXE group. In conclusion, our results suggest that estrogen regulates contraction and relaxation in the renal artery via NO synthase activity and alteration of the Ca 2+ transport systems.

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“…Prazosin is a classical antagonist which shows no subtype selectivity (Muramatsu et al, 1995;Hancock, 1996). BMY 7378 and KMD-3213 are well characterized as highly selective antagonists for alpha-1D and alpha-1A AR subtypes, respectively (Goetz et al, 1995;Shibata et al, 1995;Saussy et al, 1996;Yamagishi et al, 1996;Murata et al, 1999). Furthermore, several agonists including phenylephrine show relatively high affinity for the alpha-1D subtype (Lomasney et al, 1991;Buckner et al, 1996;Graham et al, 1996;Piascik & Perez, 2001).…”

Section: Introductionmentioning

confidence: 99%

Alpha‐1D adrenoceptors are involved in reserpine‐induced supersensitivity of rat tail artery

Taki

Tanaka

Zhang

et al. 2004

British J Pharmacology

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1 We examined reserpine-induced chemical denervation supersensitivity with special reference to alpha-1 adrenoceptor (AR) subtypes. 2 Chronic treatment with reserpine for 2 weeks depleted noradrenaline in the tail artery and spleen of rats. Noradrenaline in the thoracic aorta was negligible before and after reserpine treatment. 3 The treatment with reserpine produced supersensitivity in the contractile responses of the rat tail artery to phenylephrine, 5-HT and KCl, resulting in leftward shift of concentration-response curves (11.6-, 2.5-and 1.1-fold at EC 50 value, respectively). These results suggest a predominant sensitization of the alpha-1 AR-mediated response by reserpine treatment. 4 BMY 7378 at a concentration (30 nM) specific for blocking the alpha-1D AR subtype, but not KMD-3213 at a concentration (10 nM) selective for blocking the alpha-1A AR subtype, inhibited the supersensitivity of the phenylephrine-induced response in the reserpine-treated artery. On the other hand, the response to phenylephrine in reserpine-untreated artery was selectively inhibited by the same concentration of KMD-3213, but not by BMY 7378. Prazosin, a subtype-nonselective antagonist, blocked the responses to phenylephrine with the same potency, regardless of reserpine treatment. 5 In the thoracic aorta and spleen, no supersensitivity was produced in the responses to phenylephrine by reserpine treatment. 6 In a tissue segment-binding study using [ 3 H]-prazosin, the total density and affinity of alpha-1 ARs in the rat tail artery were not changed by treatment with reserpine. However, alpha-1D AR with high affinity for BMY 7378 was significantly detected in reserpine-treated tail artery, in contrast to untreated artery. Decreases in alpha-1A AR with high affinity for KMD-3213 and alpha-1B AR with low affinities for KMD-3213 and BMY 7378 were also estimated in reserpine-treated tail artery. 7 Alpha-1D AR mRNA in rat tail artery increased to three-folds by reserpine treatment, whereas the levels of alpha-1A and 1B mRNAs were not significantly changed. 8 The present results suggest that chronic treatment with reserpine affects the expression of alpha-1 AR subtypes of rat tail artery and that the induction of alpha-1D ARs with high affinity for catecholamines is in part associated with reserpine-induced supersensitivity.

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BMY 7378 is a selective antagonist of the D subtype of α1-adrenoceptors

Cited by 292 publications

References 5 publications

Noradrenaline contractions of human prostate mediated by α_1c‐(α_1c‐) adrenoceptor subtype

Noradrenaline contractions of human prostate mediated by α_1c‐(α_1c‐) adrenoceptor subtype

Characteristics of contractile activity in the renal artery of ovariectomized rats

Alpha‐1D adrenoceptors are involved in reserpine‐induced supersensitivity of rat tail artery

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BMY 7378 is a selective antagonist of the D subtype of α1-adrenoceptors

Cited by 292 publications

References 5 publications

Noradrenaline contractions of human prostate mediated by α1c‐(α1c‐) adrenoceptor subtype

Noradrenaline contractions of human prostate mediated by α1c‐(α1c‐) adrenoceptor subtype

Characteristics of contractile activity in the renal artery of ovariectomized rats

Alpha‐1D adrenoceptors are involved in reserpine‐induced supersensitivity of rat tail artery

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Noradrenaline contractions of human prostate mediated by α_1c‐(α_1c‐) adrenoceptor subtype

Noradrenaline contractions of human prostate mediated by α_1c‐(α_1c‐) adrenoceptor subtype