II. Experimental verification of a new model: The antagonism of β-adrenoceptor stimulants and other agonists

Brink, F.G. Van Den

doi:10.1016/0014-2999(73)90027-7

Cited by 72 publications

(21 citation statements)

References 4 publications

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“…In addition, isoprenaline was proportionally less active when the preparation was contracted with high concentrations of ACh. This may be due to functional antagonism ( Van den Brink, 1973), a phenomenon also observed with the guineapig isolated trachea model (O'Donnell & Wanstall, 1977;1978;Karlsson & Persson, 1981;Torphy et al, 1983).…”

Section: Discussionmentioning

confidence: 79%

The guinea‐pig isolated bronchus for the in vitro study of small calibre airway reactivity

Advenier

Freslon

1985

British J Pharmacology

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1 Small calibre airway reactivity to different contractile and relaxant agents was tested in vitro using small segments (about 1 mm long and 0.2 mm in internal diameter) of guinea-pig isolated intralobular bronchi. 2 EC50 values of, and maximal contractile responses to contractile agents were as follows (mean ± s.e.mean, n = 6): acetylcholine 13.6 ± 2.6 gM and 1140 ± 80 mg; histamine 5.2 ± 0.7 JM and 1094 ± 95 mg; 5-hydroxytryptamine (5-HT) 0.7 ± 0.1 gM and 595 ± 61 mg; prostaglandin Fu (PGF2.)8.8 ± 1.2 tM and 1100±88mg; tetraethylammonium 2.9±0.3mM and 1055±94mg; KC1 14.6 ± 0.5mM and 965 ± 81 mg.3 EC50 values of, and maximal relaxant responses to P-adrenoceptor stimulants on preparations precontracted with acetylcholine (1.4 x 10-4M) were: isoprenaline 0.40 ± 0.5 JM and 782 ± 65 mg, n = 18; salbutamol 0.19 ± 0.02 JM and 494 ± 55mg, n = 5; terbutaline 0.87 ± 0.18 gM and 263 ± 40mg n = 5; fenoterol 0.06 ± 0.02 JM and 722 ± 47mg, n = 5; adrenaline 0.71 ± 0.13 JM and 653 ± 62mg, n = 5; noradrenaline 10.8 ± 0.9 JM and 566 ± 97mg, n = 5.4 Differences in the maximal relaxant effects between the P-adrenoceptor stimulants showed that the preparation utilized is a relevant model for assessment of the intrinsic activity of these drugs.5 The high ratio (about 180) of the ECm for noradrenaline (pi-adrenoceptor agonist) to that for fenoterol (f2-adrenoceptor agonist), and the lack of effect of prenalterol (P1-adrenoceptor agonist) suggested that P2-adrenoceptors are preferentially involved in the relaxant activity of P-adrenoceptor stimulants in this preparation.

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Section: Discussionmentioning

confidence: 79%

The guinea‐pig isolated bronchus for the in vitro study of small calibre airway reactivity

Advenier

Freslon

1985

British J Pharmacology

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“…It follows that the activity of various bronchodilators will be dependent on the way a contractile receptor is coupled to the contractile apparatus. The potency ofPadrenoceptor agonists is known to be dependent on the degree of spontaneous tone of the airway preparation as well as the choice of spasmogen used to induce tone (Van den Brink, 1973;Jones et al, 1974;Buckner & Saini, 1975;Torphy et al, 1983;Torphy, 1984). PAdrenoceptor agonists are very effective at relaxing or preventing leukotriene-induced contractions in human (Jones et al, 1982) and guinea-pig trachea (Armour et al, 1982;Torphy et al, 1983) but are less effective on responses to cholinoceptor agonists (Torphy et al, 1983).…”

Section: Resultsmentioning

confidence: 99%

Effects of l‐serine borate on antagonism of leukotriene C₄‐induced contractions of guinea‐pig trachea

Charette

Jones

1987

British J Pharmacology

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1 The antagonist activity of three leukotriene D4 (LTD4) receptor antagonists and a number of bronchodilators was determined against LTC4-induced contractions of guinea-pig isolated tracheal chains in the absence and presence of the -y-glutamyltranspeptidase inhibitor, L-serine borate (SB).2 The LTD4 receptor antagonists FPL-55712, L-649,923 and L-648,051 effectively antagonized LTC4 responses in the absence of SB but were ineffective in the presence of 15 and/or 45 mm SB. 3 Salbutamol > isobutylmethylxanthine (IBMX) > dibutyryl cyclic AMP > aminophylline > nifedipine antagonized contractions to LTC4 in the absence of SB. In contrast, in the presence ofSB the antagonist activity of all of these agents except nifedipine was significantly reduced. The antagonist activity of the Ca2' entry blocker, nifedipine, was similar in the absence and presence of SB.4 Salbutamol and IBMX were potent functional antagonists of LTE4-induced contractions both in the absence and presence of SB. 5 These results are consistent with the hypothesis that there are contractile LTC4 receptor mechanisms in guinea-pig trachea which are unmasked by SB and are not blocked by LTD4 receptor antagonists and which are less effectively down modulated by cyclic AMP-dependent bronchodilators.

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“…This differential ability of L-arginine to reverse histamineinduced contractile responses compared with its effect on the histamine concentrationeffect curve is analogous to the inability of the beta 2 -adrenoceptor agonist, salbutamol, to shift the concentration-effect curves to acetylcholine in human bronchus at concentrations which reversed acetylcholine-induced contractile responses (10) and of the phosphodiesterase type IV inhibitor, Ro 20-1724, to shift the concentration-effect curve to capsaicin in guinea-pig isolated trachea at concentrations which reversed capsaicin-induced contractile responses (11). These findings can be explained in terms of functional antagonism (12,13). Thus, if the receptorsubeffect response relationship to L-arginine has a much lower reserve than for histamine then one may expect only minimal antagonism of the concentration-effect curve for histamine.…”

Section: Discussionmentioning

confidence: 91%

The effect of L-arginine on guinea-pig and rabbit airway smooth muscle function in vitro

Perez

Paul

Harrison

et al. 1998

Braz J Med Biol Res

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We have investigated the effects of L-arginine, D-arginine and Llysine on airway smooth muscle responsiveness to spasmogens in vitro. Both L-arginine and D-arginine (100 mM) significantly reduced the contractile potency and maximal contractile response to histamine but not to methacholine or potassium chloride in guinea-pig epithelium-denuded isolated trachea. Similarly, the contractile response to histamine was significantly reduced by L-arginine (100 mM) in rabbit epithelium-denuded isolated bronchus. The amino acid L-lysine (100 mM) failed to significantly alter the contractile potency of histamine in guinea-pig isolated trachea (P>0.05). In guinea-pig isolated trachea precontracted with histamine, both L-arginine and D-arginine produced a concentration-dependent relaxation which was not significantly altered by epithelium removal or by the presence of the nitric oxide synthase inhibitor, N G -nitro L-arginine methyl ester (L-NAME; 50 µM). Thus, at very high concentrations, arginine exhibit a noncompetitive antagonism of histamine-induced contraction of isolated airway preparations that was independent of the generation of nitric oxide and was not dependent on charge. These observations confirm previous studies of cutaneous permeability responses and of contractile responses of guinea-pig isolated ileal smooth muscle. Taken together, the data suggest that high concentrations of arginine can exert an anti-histamine effect.

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II. Experimental verification of a new model: The antagonism of β-adrenoceptor stimulants and other agonists

Cited by 72 publications

References 4 publications

The guinea‐pig isolated bronchus for the in vitro study of small calibre airway reactivity

The guinea‐pig isolated bronchus for the in vitro study of small calibre airway reactivity

Effects of l‐serine borate on antagonism of leukotriene C₄‐induced contractions of guinea‐pig trachea

The effect of L-arginine on guinea-pig and rabbit airway smooth muscle function in vitro

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II. Experimental verification of a new model: The antagonism of β-adrenoceptor stimulants and other agonists

Cited by 72 publications

References 4 publications

The guinea‐pig isolated bronchus for the in vitro study of small calibre airway reactivity

The guinea‐pig isolated bronchus for the in vitro study of small calibre airway reactivity

Effects of l‐serine borate on antagonism of leukotriene C4‐induced contractions of guinea‐pig trachea

The effect of L-arginine on guinea-pig and rabbit airway smooth muscle function in vitro

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Effects of l‐serine borate on antagonism of leukotriene C₄‐induced contractions of guinea‐pig trachea