Abstract:
:1. Experiments were performed with peptidase inhibitors on rabbit aortic strip preparations, to determine whether endogenous peptidase activity can influence the potency estimates for angiotensin receptor agonists and antagonists in this tissue. 2. Angiotensin II (A II) and angiotensin III (A III) both induced concentration-related contractions of rabbit aortic strip preparations. A III was approximately 38 fold less potent than A II, and the gradient of the A III concentration-response curve (1.00 +/- 0.04) was significantly more shallow than that (1.76 +/- 0.05) of the A II curve. 3. Neither the aminopeptidase-A and -M inhibitor, amastatin, nor the aminopeptidase-B and -M inhibitor, bestatin, affected the potency of, or the maximum response to, A II. In contrast, the potency of A III was increased by both amastatin and bestatin. Amastatin had the most marked effect and at 10 microM caused approximately a 12 fold increase in the potency of A III (EC50 values, 102 nM and 8.6 nM in the absence and presence of amastatin, respectively), and also significantly steepened the gradient of the A III concentration-response curve. Amastatin did not affect the position or shape of the concentration-response curve to the alpha 1-adrenoceptor agonist, phenylephrine. Finally, the carboxypeptidase-N inhibitor, D-L-mercaptomethyl-3-guanidine-ethylpropanoic acid (MERGETPA) did not change the position or shape of the concentration-response curves to either A II or A III.4. In the presence of amastatin, the potency of the peptide angiotensin receptor antagonist, Ile7-A III (100nM-l microM ), was increased approximately 13 fold (pA2, with A II as the agonist, 7.0 +/- 0.1 and 8.1 +/- 0.1, in the absence and presence of amastatin, respectively). However, the potency of the nonpeptide angiotensin receptor antagonist, DuP 753 (30-300 nM), was little affected by amastatin (pA2, 8.2 +/- 0.1 and 8.1 +/- 0.1 in the absence and presence of amastatin, respectively).5. The results of this study suggest that endogenous aminopeptidase activity in the rabbit thoracic aorta can profoundly affect estimates of the potency of peptide angiotensin receptor agonists and antagonists.A suitable aminopeptidase inhibitor should therefore be included in studies, using this tissue, which aim to classify angiotensin receptor subtype(s) based on the rank order of peptide angiotensin receptor agonist and/or antagonist potencies.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Robertson MJ,Cunoosamy MP,Clark KLdoi
10.1111/j.1476-5381.1992.tb14310.xsubject
Has Abstractpub_date
1992-05-01 00:00:00pages
166-72issue
1eissn
0007-1188issn
1476-5381journal_volume
106pub_type
杂志文章abstract::Opioid drugs such as morphine and meperidine are widely used in clinical pain management, although they can cause some adverse effects. A number of studies indicate that N-methyl-D-aspartate (NMDA) receptors may play a role in the mechanism of morphine analgesia, tolerance and dependence. Being an antitussive with NMD...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0706086
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb08470.x
更新日期:1978-03-01 00:00:00
abstract::1. This study tested the hypothesis that the systemic effects of burn include altered metabolic activity in the heart. Metabolic activity was studied by measuring alterations in cyclic nucleotide levels and protein concentrations in atrial and ventricular muscle in mice at 14 and 22 days after a 20% body surface area ...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1990.tb12698.x
更新日期:1990-10-01 00:00:00
abstract::1. The effects of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) on the ionic currents of rat carotid body type I cells were investigated by use of whole-cell and outside-out patch clamp techniques. 2. NDGA (5-50 microM) produced a concentration-dependent inhibition of whole-cell K+ currents at all activa...
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journal_title:British journal of pharmacology
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abstract::1. SB 206553 (5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2 ,3-f]indole) displays a high affinity (pK1 7.9) for the cloned human 5-HT2C receptor expressed in HEK 293 cells and the 5-HT2B receptor (pA2 8.9) as measured in the rat stomach fundus preparation. SB 206553 has low affinity for cloned human 5-HT...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15208.x
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abstract::1. Conscious, Long Evans rats (n = 10), chronically instrumented for the measurement of regional haemodynamics, were studied on 3 consecutive experimental days to assess responses to angiotensin II (AII) (125 pmol kg-1, i.v.) and noradrenaline (1 nmol kg-1, i.v.) in the absence and presence of the AT2-receptor antagon...
journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb08471.x
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更新日期:1999-09-01 00:00:00
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更新日期:2008-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb09036.x
更新日期:1992-03-01 00:00:00
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1989.tb14635.x
更新日期:1989-11-01 00:00:00
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doi:10.1111/j.1476-5381.1986.tb10186.x
更新日期:1986-03-01 00:00:00
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doi:10.1038/sj.bjp.0704185
更新日期:2001-08-01 00:00:00
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更新日期:2004-10-01 00:00:00
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更新日期:1976-05-01 00:00:00
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更新日期:1998-05-01 00:00:00
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更新日期:2020-04-01 00:00:00
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更新日期:1983-01-01 00:00:00