The alkylating prazosin analog SZL 49 inactivates both α1A- and α1B-adrenoceptors

Mante, Saakwa; Minneman, Kenneth P.

doi:10.1016/0922-4106(91)90061-l

Cited by 15 publications

(2 citation statements)

References 7 publications

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“…The rate constants for association and dissociation were 0.011 0.004 nM-'min-' and 0.061 ± 0.012 min 1, respectively (n = 4). The calculated dissociation constant from kinetic data was estimated to be 4.97 ± 0.86 nM (n = 4), a value similar to that obtained from equilibrium binding experiments (Figure 1) (Minneman, 1988;Mante & Minneman, 1991). Pretreatment with increasing doses of CEC (10 to 5011M) caused a concentrationdependent loss of high-affinity binding sites without any significant effect on apparent prazosin affinity.…”

Section: High-and Low-affinity Binding Sites For [3h]-prazosin In Vassupporting

confidence: 48%

Relation between α₁‐adrenoceptor subtypes and noradrenaline‐induced contraction in rat portal vein smooth muscle

Sayet

Neuilly

Rakotoarisoa

et al. 1993

British J Pharmacology

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1 In vascular smooth muscle, a,-adrenoceptors have been classified recently into two or three subtypes. We examined which xl-adrenoceptor subtypes are involved in the noradrenaline-induced contraction of rat portal vein smooth muscle.2 Binding studies with [3H]-prazosin in membranes from equine portal vein smooth muscle revealed the presence of two distinct affinity binding sites. The high-affinity site for [3H]-prazosin was also identified in intact strips of rat portal vein. Prazosin, HV723 (o-ethyl-3,4,5-trimethoxy-a-(3-((2-(2-methoxyphenoxy)ethyl)-amino)-propyl) benzene-acetonitrile fumarate), WB4101 (2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane), 5-methylurapidil, phentolamine and yohimbine antagonized[3H]-prazosin binding at both types of sites. Pretreatment with 50 jAM chloroethylclonidine (CEC) eliminated the high-affinity sites for prazosin but had no effect on the low-affinity sites. 3 Noradrenaline produced a concentration-dependent contraction in the rat portal vein. Pretreatment with 50 JAM CEC induced a slight rightward displacement of the concentration-response curve but the maximal contraction was not significantly affected suggesting that the CEC-sensitive xl-adrenoceptors played a minor role in the noradrenaline-induced contraction. Prazosin, WB4101 and HV723 produced a concentration-dependent inhibition of noradrenaline-induced contractions. The inhibition curves were little affected by CEC-pretreatment and yielded a relative order of potency of WB4101 > prazosin > HV723. 4 In the presence of 0.1 jAM isradipine to block voltage-dependent Ca2+ channels, the noradrenalineinduced contraction is due to release of Ca2+ ions from agonist-sensitive intracellular Ca2+ stores. Under these conditions, the noradrenaline-induced contraction was not significantly affected by pretreatment with 50 JAM CEC but was inhibited by the antagonists mentioned above with affinities different from those in the absence of isradipine. The rank order of potency became HV723 > WB4101 > prazosin. 5 The present results indicate the existence of two distinct o1-adrenoceptor subtypes in rat portal vein smooth muscle, which show high-and low-affinities respectively for each of prazosin, WB4101 and HV723 and correspond to alH-and 'XlL-adrenoceptor subtypes. According to recent a,-adrenoceptor subclassifications, the alH-adrenoceptor subtype which is sensitive to inactivation by CEC may correspond to the MtB-adrenoceptor subtype. The contraction induced by noradrenaline seems to be predominantly mediated through the alL-adrenoceptor subtypes which may include the MIN-adrenoceptor subtype, as recently proposed.

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Section: High-and Low-affinity Binding Sites For [3h]-prazosin In Vassupporting

confidence: 48%

Relation between α₁‐adrenoceptor subtypes and noradrenaline‐induced contraction in rat portal vein smooth muscle

Sayet

Neuilly

Rakotoarisoa

et al. 1993

British J Pharmacology

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“…CGP 12177 (51) has been shown to be a partial agonist at the native /83-adrenoceptor found in mammalian adipocytes from several species. 31 In CHO cells expressing recombinant human /83-adrenoceptors, other phenoxypropanolamines, such as tertatolol (52) and carazolol (53), produce a maximum response that is greater than that produced by CGP 12177 and equivalent to that produced by isoproterenol.12 Other phenoxypropanolamines, such as ICI 198,157 (54) and its metabolite, ICI 201,651 (55), have been reported to be selective /83-adrenoceptor agonists. 1.1.4. Imidazolines and Imidazolidines.…”

Section: Och3 Hn' Nh2mentioning

confidence: 99%

.alpha.- and .beta.-Adrenoceptors: From the Gene to the Clinic. 2. Structure-Activity Relationships and Therapeutic Applications

Rr¹,

Bondinell²,

Jp³

1995

J. Med. Chem.

182

135

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?1 Adrenoceptor subtypes: A synopsis of their pharmacology and molecular biology

Hancock

1996

Drug Dev. Res.

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The alkylating prazosin analog SZL 49 inactivates both α1A- and α1B-adrenoceptors

Cited by 15 publications

References 7 publications

Relation between α₁‐adrenoceptor subtypes and noradrenaline‐induced contraction in rat portal vein smooth muscle

Relation between α₁‐adrenoceptor subtypes and noradrenaline‐induced contraction in rat portal vein smooth muscle

.alpha.- and .beta.-Adrenoceptors: From the Gene to the Clinic. 2. Structure-Activity Relationships and Therapeutic Applications

?1 Adrenoceptor subtypes: A synopsis of their pharmacology and molecular biology

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The alkylating prazosin analog SZL 49 inactivates both α1A- and α1B-adrenoceptors

Cited by 15 publications

References 7 publications

Relation between α1‐adrenoceptor subtypes and noradrenaline‐induced contraction in rat portal vein smooth muscle

Relation between α1‐adrenoceptor subtypes and noradrenaline‐induced contraction in rat portal vein smooth muscle

.alpha.- and .beta.-Adrenoceptors: From the Gene to the Clinic. 2. Structure-Activity Relationships and Therapeutic Applications

?1 Adrenoceptor subtypes: A synopsis of their pharmacology and molecular biology

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Relation between α₁‐adrenoceptor subtypes and noradrenaline‐induced contraction in rat portal vein smooth muscle

Relation between α₁‐adrenoceptor subtypes and noradrenaline‐induced contraction in rat portal vein smooth muscle