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A pharmacological differentiation between postjunctional (AT1A) and prejunctional (AT1B) angiotensin II receptors in the rabbit aorta

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Abstract

The effects of angiotensin II and angiotensin III were compared at prejunctional and postjunctional AT1 receptors of the rabbit thoracic aorta. Furthermore, the influence of PD123319, losartan and eprosartan on these effects was also compared. To study prejunctional effects, the tissues were preincubated with (3H)-noradrenaline, superfused and electrically stimulated (1 Hz, 2 ms, 50 mA, 5 min). To study postjunctional effects, non-cumulative concentration–response curves were determined. Both angiotensin II and angiotensin III were more potent prejunctionally than postjunctionally. In the case of angiotensin II, the EC50 was 12 times lower at the prejunctional than at the postjunctional level, while that of angiotensin III was 30 times lower prejunctionally. Furthermore, whereas angiotensin II was about 33 times more potent than angiotensin III postjunctionally, it was only 12 times more potent than angiotensin III prejunctionally. Eprosartan did not differentiate between prejunctional and postjunctional effects of both angiotensins. In contrast, PD123319 and losartan did differentiate; however, whereas PD123319 concentration-dependently antagonised the facilitation of tritium release caused by angiotensin II and angiotensin III and had no influence on the contraction of the aortic rings elicited by the peptides, losartan did the opposite: it concentration-dependently antagonised the contractions caused by the peptides on the aortic rings and exerted no influence on the facilitatory effect of angiotensin II and angiotensin III. These results show that prejunctional and postjunctional receptors for angiotensin II and angiotensin III are different and underline the hypothesis that postjunctional AT1 receptors belong to the AT1A subtype, while prejunctional AT1 receptors belong to the AT1B subtype.

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Acknowledgements

This work was supported by Project POCTI/FCB/40832/2001. The experiments complied with Portuguese current law.

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Authors and Affiliations

  1. Faculdade de Medicina, Instituto de Farmacologia e Terapêutica, Alameda Hernani Monteiro, 4200-319, Porto, Portugal

    Serafim Guimarães, Catarina Carneiro, Fernando Brandão, António Albino-Teixeira & Daniel Moura

  2. Faculdade de Farmácia, Laboratório de Farmacologia, Rua Aníbal Cunha, 136, 4050, Porto, Portugal

    Helder Pinheiro

Authors
  1. Serafim Guimarães
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  2. Catarina Carneiro
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  3. Fernando Brandão
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  4. Helder Pinheiro
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  5. António Albino-Teixeira
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  6. Daniel Moura
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Correspondence to Serafim Guimarães.

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Guimarães, S., Carneiro, C., Brandão, F. et al. A pharmacological differentiation between postjunctional (AT1A) and prejunctional (AT1B) angiotensin II receptors in the rabbit aorta. Naunyn-Schmiedeberg's Arch Pharmacol 370, 262–269 (2004). https://doi.org/10.1007/s00210-004-0977-7

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  • DOI: https://doi.org/10.1007/s00210-004-0977-7

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