Characteristics of adrenoceptors and [3H]nitrendipine receptors of porcine vascular smooth muscle: differences between coronary artery and aorta.

Nishimura, Junji; Kobayashi, Hideo; Nakamura, Motoomi

doi:10.1161/01.res.60.6.837

Cited by 22 publications

(8 citation statements)

References 47 publications

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“…Using the selective M2-adrenoceptor antagonist [3H]-RX821002, there were no differences in the Kd values but the density of [3H]-RX821002 binding was highest in the TA and MEV followed by the PLV, then the EA, and low densities of [3H]-RX821002 binding being found in the PCDA and SA. In agreement with Nishimura et al (1987), the TA has a high density of both a,-and M2-adrenoceptor binding sites, with the density of a2-adrenoceptor sites being slightly greater than that of al-adrenoceptor sites. The densities of these sites found in this study are 30% less than those reported by Nishimura et al (1987), possibly as a result of their further purification of the PNS fraction, but the ratio of Ml-:M2-adrenoceptor sites (this study: 1:1.4; Nishimura et al: 1:1.9) is very similar.…”

Section: Saturation Studies In Other Porcine Blood Vesselssupporting

confidence: 71%

“…In agreement with Nishimura et al (1987), the TA has a high density of both a,-and M2-adrenoceptor binding sites, with the density of a2-adrenoceptor sites being slightly greater than that of al-adrenoceptor sites. The densities of these sites found in this study are 30% less than those reported by Nishimura et al (1987), possibly as a result of their further purification of the PNS fraction, but the ratio of Ml-:M2-adrenoceptor sites (this study: 1:1.4; Nishimura et al: 1:1.9) is very similar. In the other vascular tissues studied it would appear that both in the SA and PCDA there is a predominance (although small) of al-adrenoceptor binding sites, the reverse of which is observed both in the PLV and MEV (i.e.…”

Section: Saturation Studies In Other Porcine Blood Vesselssupporting

confidence: 71%

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The relationship between density of α‐adrenoceptor binding sites and contractile responses in several porcine isolated blood vessels

Wright

Blaylock

Kendall

et al. 1995

British J Pharmacology

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1 The aim of this study was to investigate constrictor x-adrenoceptors in three isolated blood vessles of the pig, the thoracic aorta (TA), the splenic artery (SA) and marginal ear vein (MEV) and then compare the functional response with the densities of a,-and M2-adrenoceptor binding sites in these and several other porcine vascular tissues, palmar common digital artery (PCDA), palmar lateral vein (PLV) and ear artery (EA).2 Noradrenaline (NA), phenylephrine (PE) and UK14304 (all at 0.03-10gM) elicited concentrationdependent contractions in the TA and MEV, with a rank order of potency of UK14304>NA>PE. UK14304 produced maximal responses which were 58% (TA) and 65% (MEV) of that of NA. In the SA, UK14304 and PE produced maximal responses which were less than 10% and 50% of the NA-induced maximal response respectively, with an order of potency of NA>PE. In the SA, NAinduced contractions were competitively antagonized by prazosin (pA2 = 8.60 ± 0.15). Further, rauwolscine (1-1O M) antagonized NA-induced contractions with an apparent pKB of 6.09 ± 0.11 (n = 6), indicating an action at al-adrenoceptors. The combination of the two antagonists at concentrations selective for al-(0.1 JLM) and a2-adrenoceptors (1 J4M) had no greater effect than either antagonist alone.This suggests that the SA expresses only post-junctional a1-adrenoceptors.3 In the TA, prazosin produced non-parallel shifts in the NA-induced CRC and this was also observed with rauwolscine, where reductions in the maximal responses were also observed. In the MEV, prazosin was largely inactive in antagonizing NA-induced contractions. In both these vessels a combination of these two antagonists had a greater effect than either alone, indicating the presence of functional a,-and M2-adrenoceptors. The post-junctional x2-adrenoceptors in all of these vessels were resistant to prazosin, suggesting the a2-adrenoceptor to be of the a2A/2D subtype. mg-', n = 4), followed by the PCDA (256.7 ± 22.7 fmol mg', n = 4), the PLV and SA having approximately equal density (143.6 ± 3.9 and 159.1 ± 7.0 fmol mg-' respectively, n = 4 for both), followed by the EA (91.3 ± 10.5 fmol mg-', n = 3) and the MEV had the lowest density (48.9 ± 11.4 fmol mg-', n = 3).7 In saturation studies using [3H]-RX821002, all tissues produced single site saturation curves with no differences in the Kd values (range 1.31 ± 2.16 nM) but the highest densities were found in the TA and MEV (545.3 ± 36.2 and 531.0 ± 40.9 fmol mg-' respectively), followed by the PLV (418.4 ± 39.4 fmol mg-'), then the EA (266.3 ± 40.0 fmol mg-'), and low densities of [3H]-RX821002 binding being found in the PCDA and SA (155.9 ± 18.1 and 117.5 ± 19.3 fmol mg-' respectively). 8 The pattern of binding site distribution for ol-and C2-adrenoceptors is in reasonable agreement with functional studies carried out in these porcine vascular tissues; the TA has the highest densities of a,-and X2-adrenoceptors; in the SA and PCDA there is a predominance (although small) of al-adrenoceptor binding sites, the reverse of which is obse...

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Section: Saturation Studies In Other Porcine Blood Vesselssupporting

confidence: 71%

Section: Saturation Studies In Other Porcine Blood Vesselssupporting

confidence: 71%

The relationship between density of α‐adrenoceptor binding sites and contractile responses in several porcine isolated blood vessels

Wright

Blaylock

Kendall

et al. 1995

British J Pharmacology

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“…Figure 2 demonstrates this with two individual ligands (CGP20712A and ICI118551) which are highly selective for the human β1 and β2-adrenoceptors respectively. Interestingly this species effect is seen elsewhere - ICI118551, whilst having high affinity for the human β2-adrenoceptor has lower affinity for the porcine β2-adrenoceptor [32]–[34].…”

Section: Discussionmentioning

confidence: 74%

A Full Pharmacological Analysis of the Three Turkey β-Adrenoceptors and Comparison with the Human β-Adrenoceptors

Baker

2010

PLoS ONE

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BackgroundThere are three turkey β-adrenoceptors: the original turkey β-adrenoceptor from erythrocytes (tβtrunc, for which the X-ray crystal structure has recently been determined), tβ3C and tβ4C-receptors. This study examined the similarities and differences between these avian receptors and mammalian receptors with regards to binding characteristics and functional high and low affinity agonist conformations.Methodology/Principal FindingsStable cell lines were constructed with each of the turkey β-adrenoceptors and 3H-CGP12177 whole cell binding, CRE-SPAP production and 3H-cAMP accumulation assays performed. It was confirmed that the three turkey β-adrenoceptors are distinct from each other in terms of amino acid sequence and binding characteristics. The greatest similarity of any of the turkey β-adrenoceptors to human β-adrenoceptors is between the turkey β3C-receptor and the human β2-adrenoceptor. There are pharmacologically distinct differences between the binding of ligands for the tβtrunc and tβ4C and the human β-adrenoceptors (e.g. with CGP20712A and ICI118551). The tβtrunc and tβ4C-adrenoceptors appear to exist in at least two different agonist conformations in a similar manner to that seen at both the human and rat β1-adrenoceptor and human β3-adrenoceptors. The tβ3C-receptor, similar to the human β2-adrenoceptor, does not, at least so far, appear to exist in more than one agonist conformation.Conclusions/SignificanceThere are several similarities, but also several important differences, between the recently crystallised turkey β-adrenoceptor and the human β-adrenoceptors. These findings are important for those the field of drug discovery using the recently structural information from crystallised receptors to aid drug design. Furthermore, comparison of the amino-acid sequence for the turkey and human adrenoceptors may therefore shed more light on the residues involved in the existence of the secondary β-adrenoceptor conformation.

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“…Thus, it remains to be elucidated how nipradilol-and/or the nitroglycerin-cyclic GMP-mediated mechanism controls the influx and the efflux of Ca2+ through the sarcolemmal membrane in relaxation of the vascular smooth muscle. We have previously reported that the proximal portion of the porcine coronary artery is /3-adrenoceptor dominant (Nishimura et al, 1987), and activation of these receptors by isoprenaline results in a reduction of cytosolic calcium concentrations (Shogakiuchi et al, 1991;Ushio-Fukai et al, 1993). Isoprenaline relaxes almost all varieties of smooth muscle by increases in the intracellular cyclic AMP levels due to the activation of adenylate cyclase (Bulbring & Tomita, 1987).…”

Section: Discussionmentioning

confidence: 99%

Some effects of nipradilol, a β‐antagonist possessing a nitroxy group, on smooth muscle of the pig coronary artery

Abe

Nakamura

Kobayashi

1996

British J Pharmacology

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1 The effects of nipradilol, a ,B-adrenoceptor antagonist which possesses a nitroxy group, on cytosolic Ca2+ concentration ([Ca2+i) and on tension development were simultaneously measured by front-surface fluorometry and fura-2-loaded strips in the proximal portion of pig coronary arteries.2 Nipradilol reduced in a concentration-dependent manner both the [Ca2+]i and tension, irrespective of whether the strips were unstimulated or exposed to either high K+ or histamine containing solutions. However, both in the case of contractions induced by high K+-depolarization and histamine stimulation, for a given [Ca2+]i elevation the tension which developed in the presence of nipradilol was smaller than that generated in its absence, so that the [Ca2 +]i-tension curves during the contraction were shifted to the right.3 In the absence of extracellular Ca2 , the [Ca2i], elevation due to the release of Ca2+ from histaminesensitive store was inhibited by nipradilol. Nipradilol had no effect on the [Ca2+]i elevation due to the release of Ca2+ from caffeine-sensitive stores; however, it did inhibit the caffeine-induced increase in tension. A derivative of nipradilol, which lacked a nitroxy molecule (Nip(-N)), had no effect on the At lower concentrations, nipradilol acted as a fl-blocker, the IC50 value being smaller than that of Nip(-N), and at higher concentrations, it acted as a nitrovasodilator. 5 Thus, it is suggested that, at lower concentrations, nipradilol, an antianginal drug, acts as a ,Badrenoceptor antagonist. At higher concentrations, it relaxes the proximal portion of the coronary artery by directly reducing [Ca2']i and the Ca2+-sensitivity of the myofilaments, apparently due to the presence of the nitroxy molecule.

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Characteristics of adrenoceptors and [3H]nitrendipine receptors of porcine vascular smooth muscle: differences between coronary artery and aorta.

Cited by 22 publications

References 47 publications

The relationship between density of α‐adrenoceptor binding sites and contractile responses in several porcine isolated blood vessels

The relationship between density of α‐adrenoceptor binding sites and contractile responses in several porcine isolated blood vessels

A Full Pharmacological Analysis of the Three Turkey β-Adrenoceptors and Comparison with the Human β-Adrenoceptors

Some effects of nipradilol, a β‐antagonist possessing a nitroxy group, on smooth muscle of the pig coronary artery

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