Differences Between Rat and Guinea Pig Aorta in Postreceptor Mechanisms of α1-Adrenoceptors

Jenkin, R. A.; Baldi, M.; Iwanov, V.; Moulds, R. F. W.

doi:10.1097/00005344-199110000-00013

Cited by 10 publications

(14 citation statements)

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“…The sustained component of NA-produced contraction of guinea-pig aorta has a unique characteristic that it is resistant to the blockade by organic Ca 2+ entry blockers such as nifedipine, diltiazem and verapamil (Gouw et al 1990;Jenkin et al 1991;Saito et al 1998). By comparison, these Ca 2+ entry blockers have been shown to largely attenuate both sustained tension development and Ca 2+ entry produced by NA in rat aorta (Godfraind 1983;Sato et al 1988;Jenkin et al 1991;Saito et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Ca 2+ entry channels responsible for mechanical responses of guinea-pig aorta to noradrenaline and thapsigargin using SK&F 96365 and LOE 908

Tanaka

Imai

Igarashi

et al. 2000

Naunyn-Schmiedeberg's Archives of Pharmacology

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Noradrenaline (NA) produces sustained contractions in conduit arteries such as aorta isolated from various animal species. In guinea-pig aorta, NA-produced sustained contraction is largely dependent upon the influx of extracellular Ca2+, but is refractory to the treatment with organic Ca2+ entry blockers. In the present study, we attempted to characterize pharmacologically the Ca2+ entry channel responsible for NA-produced sustained contraction of guinea-pig aorta using SK&F 96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenylethyl]-1H-imi dazole) and LOE 908 ((R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-[2- (2,3,4-trimethoxyphenyl)ethyl]-acetamide), both of which block voltage-independent Ca2+ channels. The effects of SK&F 96365 and LOE 908 on NA-produced contraction were compared with those on extracellular Ca2+-dependent contractile and endothelium-dependent relaxant responses to thapsigargin (TSG), an inhibitor of Ca2+-pump Ca2+-ATPase. NA (3x10(-6) M)-produced sustained contraction of guinea-pig aorta without endothelium exhibited a strong dependency on the extracellular Ca2+. Nicardipine (10(-7) M), diltiazem (10(-5) M) and verapamil (10(-5) M) did not show any appreciable inhibitory effects on NA-produced sustained contraction. SK&F 96365 concentration-dependently (10(-6)-10(-4) M) attenuated the NA-produced sustained contraction whereas LOE 908 did not affect it at concentrations up to 10(-4) M. Similarly, extracellular Ca2+-dependent contraction of guinea-pig aorta without endothelium in response to TSG was also diminished by SK&F 96365 but was unaffected by LOE 908. In fura-PE3-loaded vascular preparations, SK&F 96365 decreased both cytoplasmic Ca2+ level ([Ca2+]i) and muscle tension elevated by NA and TSG. Both SK&F 96365 and LOE 908 did not affect an endothelium-dependent relaxation of guinea-pig aorta in response to TSG. These findings suggest that in guinea-pig aortic smooth muscle cells, NA activates Ca2+ influx across the plasma-membrane through the Ca2+-permeable channel which is identical with or has similar properties to the store-operated Ca2+ channel (SOCC) stimulated by TSG, but is distinct from endothelial cell SOCC.

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Section: Introductionmentioning

confidence: 99%

Comparison of the Ca 2+ entry channels responsible for mechanical responses of guinea-pig aorta to noradrenaline and thapsigargin using SK&F 96365 and LOE 908

Tanaka

Imai

Igarashi

et al. 2000

Naunyn-Schmiedeberg's Archives of Pharmacology

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“…Over the past 40 years, experimental studies on isolated for contraction (Beckeringh et al, 1984;Jenkin et al, 1991) blood vessels from standard laboratory animals, e.g. rat, and the pharmacological characteristics of a-adrenoceptors rabbit, guinea-pig and, less commonly, cat, dog and Nielsen et al, primates, have yielded invaluable information on the proper-1991).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological characterization of noradrenaline‐induced contractions of the porcine isolated palmar lateral vein and palmar common digital artery

Blaylock

Wilson

1995

British J Pharmacology

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The aim of this study was to examine the pharmacological characteristics of α‐adrenoceptor‐mediated contractions in two porcine isolated blood vessels, the palmar lateral vein (PLV) and the palmar common digital artery (PCDA). This was carried out with noradrenaline used as the agonist throughout, and either phentolamine (non‐selective α‐adrenoceptor antagonist), prazosin and YM‐12617 (selective α1‐adrenoceptor antagonists) or rauwolscine and CH‐38083 (selective α2‐adrenoceptor antagonists). Noradrenaline (0.003–10 μm) produced concentration‐dependent contractions in both vessels, with the PCDA (pD2 = 6.33 ± 0.07, n = 10) being approximately 10 fold less sensitive to noradrenaline compared to the PLV (pD2 = 7.39 ± 0.09, n = 8). Also, the maximal response to noradrenaline was greater in the PCDA compared to the PLV. Phentolamine (0.03–30 μm) produced parallel rightward shifts in the CRC to noradrenaline in both tissue preparations. The pA2 values were similar and slopes of the Schild plots were not significantly different from unity, indicating an interaction between phentolamine and a single receptor in each preparation. In the PCDA the α1‐adrenoceptor antagonists, prazosin (0.01–1 μm) and YM‐12617 (0.01–1μm) produced non‐parallel rightwards shifts in the CRC to noradrenaline, with the lower 10–15% of the CRC exhibiting greater resistance to the effects of these antagonists compared to the upper part. In contrast, rauwolscine (1–10 μm) and CH‐38083 (10 μm) produced parallel displacement of the CRC to noradrenaline. In the PLV, low concentrations of either α1‐ (0.01 μm) or α2‐adrenoceptor antagonists (0.1–1 μm) produced a large shift in the CRC, but subsequent higher concentrations had only small additional effects. Based upon pKB values estimated from the effects of the lower concentrations of antagonists, the results are consistent with a large population of α1‐adrenoceptors in the PCDA and a mixture of α1‐ and α2‐adrenoceptors in the PLV. In both tissues, when an α1‐ and an α2‐adrenoceptor antagonist were used in combination the effect produced was greater than that with either agent alone. In contrast, the combination of the α1‐adrenoceptor antagonists (prazosin and YM‐12617 together) or the α2‐adrenoceptor antagonists (CH‐38083 and rauwolscine together) were no more effective than that produced by the individual antagonists. These findings suggest the presence of functional α1‐ and α2‐adrenoceptors in the PLV and PCDA. Phenoxybenzamine (0.3–3 μm, 60 min exposure) produced a concentration‐dependent reduction in the maximal response to noradrenaline which was more pronounced in the PCDA than the PLV. After a 60 min exposure to a combination of phenoxybenzamine (1 μm) and rauwolscine (1 μm), the remaining NA‐induced contraction after washout was resistant to prazosin (0.1 μm) and sensitive to rauwolscine (1 μm) in both tissue preparations, indicating the existence of functional α2‐adrenoceptors in both vessels. Evidence suggests that post‐junctional α1‐ and α2‐adrenoceptors contribute to noradrenaline‐induced c...

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“…In guinea-pig aorta, contraction induced by noradrenaline depends mainly upon release of intracellular Ca2`through PI pathway activation without participation of extracellular Ca2+-entry through voltage-dependent calcium channels (Jenkin et al, 1991). The a-adrenceptor responsible for this contraction has been identified as aIA- (Oriowo, 1994) or alBsubtype (Veenstra et al, 1992 (Godfraind et al, 1986) and, in some vascular tissues, like rat aorta, it has been demonstrated that high K+ even induces catecholamine A release from sympathetic terminal nerves (Ivorra et al, 1993a).…”

Section: Discussionmentioning

confidence: 99%

“…The aIadrenoceptor present in the guinea-pig aorta has been defined as either an a1A- (Oriowo, 1994;Oriowo & Ruffolo, 1992) or alB-subtype (Oriowo & Ruffolo, 1992;Veenstra et al, 1992), both of them couple to the release of intracellular Ca2+ through an increased production of inositol phosphates (Jenkin et al, 1991 Analysis of the action of S-( + )-boldine on the formation of [3H]-inositol phosphates induced by noradrenaline 10 uM in the guinea-pig aorta shows that this benzylisoquinoline alkaloid, at a concentration of 30 gM which relaxes almost completely the NA-induced contraction of the guinea-pig aorta, is able to block the PI formation pathway linked to ac-adrenoceptor activation. These data support the hypothesis that S-(+)-boldine is an ac-adrenoceptor antagonist in guinea-pig aorta acting on a homogeneous receptor population and, also, corroborate the fact that a1-adrenoceptor activation causes phosphoinositide hydrolysis in this tissue.…”

Section: Discussionmentioning

confidence: 99%

“…The aim of the present work was, firstly, to investigate the antagonist activity of S-(+)-boldine on the a,-adrenoceptor present in the guinea-pig aorta by use of functional experiments and, secondly, to study the influence of S-( + )-boldine on the phosphoinositide (PI) pathway in this tissue by direct determination of total [3H]-inositol phosphates accumulation, since activation of a,-adrenoceptors in guinea-pig aorta implies activation of the PI pathway (Jenkin et al, 1991). The relaxant activity of S-(+)-boldine was compared with that of papaverine.…”

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confidence: 99%

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The effect of S‐(+)‐boldine on the α₁‐adrenoceptor of the guinea‐pig aorta

Chuliá

Moreau

Naline

et al. 1996

British J Pharmacology

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1 The cardiovascular activity of S-( + )-boldine, an aporphine alkaloid structurally related to papaverine, was determined. The was not affected by a 60 min incubation period with different doses of S-( + )-boldine (1-300 gM). Papaverine inhibited partially this caffeine-induced contraction at the maximal dose used (100 gM). 5 Inositol phosphates formation induced by noradrenaline (10 gM) in guinea-pig thoracic aorta was inhibited by S-(+)-boldine (30 gM) but not by papaverine (10 gM). 6 Contractions of guinea-pig trachea caused by acetylcholine (100 gM) or histamine (10 gM) were not modified by S-(+)-boldine (0.1-100 gM). 7 These results provide evidence that S-(+)-boldine, an aporphine alkaloid, has interesting properties as an a,-adrenoceptor blocker in vascular smooth muscle, and acts as a competitive antagonist of the a,-adrenoceptor present in the guinea pig aorta.

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Differences Between Rat and Guinea Pig Aorta in Postreceptor Mechanisms of α1-Adrenoceptors

Cited by 10 publications

References 0 publications

Comparison of the Ca 2+ entry channels responsible for mechanical responses of guinea-pig aorta to noradrenaline and thapsigargin using SK&F 96365 and LOE 908

Comparison of the Ca 2+ entry channels responsible for mechanical responses of guinea-pig aorta to noradrenaline and thapsigargin using SK&F 96365 and LOE 908

Pharmacological characterization of noradrenaline‐induced contractions of the porcine isolated palmar lateral vein and palmar common digital artery

The effect of S‐(+)‐boldine on the α₁‐adrenoceptor of the guinea‐pig aorta

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Differences Between Rat and Guinea Pig Aorta in Postreceptor Mechanisms of α1-Adrenoceptors

Cited by 10 publications

References 0 publications

Comparison of the Ca 2+ entry channels responsible for mechanical responses of guinea-pig aorta to noradrenaline and thapsigargin using SK&F 96365 and LOE 908

Comparison of the Ca 2+ entry channels responsible for mechanical responses of guinea-pig aorta to noradrenaline and thapsigargin using SK&F 96365 and LOE 908

Pharmacological characterization of noradrenaline‐induced contractions of the porcine isolated palmar lateral vein and palmar common digital artery

The effect of S‐(+)‐boldine on the α1‐adrenoceptor of the guinea‐pig aorta

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The effect of S‐(+)‐boldine on the α₁‐adrenoceptor of the guinea‐pig aorta