Postjunctional supersensitivity and subsensitivity of excitable tissues to drugs

Fleming, William W.; McPhillips, Joseph J.; Westfall, David P.

doi:10.1007/3-540-06238-6_5

Cited by 90 publications

(6 citation statements)

References 80 publications

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“…The above examples illustrate multiple associations between an increase in "prejunctional" stimuli of airway narrowing and bronchial hypersensitivity, which is in support of theoretical analyses [20,21). It is obvious that removal of the mediators and neurotransmitters, by enzymatic breakdown or absorption into the circulation, is an important determinant of the effect of these stimuli.…”

Section: Hypersensitivity: Shift Of the Dose-response Curvesupporting

confidence: 68%

“…The theoretical aspects of the position and maximal response of dose-response curves have been elegantly worked out by MoRENO et al [20] in 1986. They applied knowledge of the pharmacology of doseresponse curves in vitro [21] to the curves of airway narrowing observed in vivo. A leftward shift of the curve can be regarded as being the result of any augmentation of the airway narrowing stimuli ("prejunctional" mechanisms) [20,21].…”

Section: Shape Of Dose-response Curvesmentioning

confidence: 99%

“…They applied knowledge of the pharmacology of doseresponse curves in vitro [21] to the curves of airway narrowing observed in vivo. A leftward shift of the curve can be regarded as being the result of any augmentation of the airway narrowing stimuli ("prejunctional" mechanisms) [20,21]. On the other hand, upward movement of the maximal response plateau is theoretically the result of any increase in the response of the effector organ ("postjunctional" mechanisms) [20,21].…”

Section: Shape Of Dose-response Curvesmentioning

confidence: 99%

“…A leftward shift of the curve can be regarded as being the result of any augmentation of the airway narrowing stimuli ("prejunctional" mechanisms) [20,21]. On the other hand, upward movement of the maximal response plateau is theoretically the result of any increase in the response of the effector organ ("postjunctional" mechanisms) [20,21]. In the following, we have compiled recent experimental evidence in favour and against a separate role of "pre-and postjunctional" mechanisms in human bronchial hyperresponsiveness in vivo.…”

Section: Shape Of Dose-response Curvesmentioning

confidence: 99%

“…It could be altered by rcceptor regulation [51], propagation of excitation (through gap junctions) [43], smooth muscle mass, (e.g. hypertrophy and hyperplasia) [50), resting membrane potential [21,50), calcium handling [21,50], crossbridges cycling 1501 or length-tension characteristics [20, 501. Most of these factors have not been addressed systematically with regard to the in vivo maximal response in man. In animals it has been observed that sensitized smooth muscle in vitro shows increased isotonic shortening due to a reduction in so-called internal resistance, associated with enhanced velocity of shortening [52).…”

Section: Excessive Airway Narrowing: Lift Of the Maximal Responsementioning

confidence: 99%

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Bronchial hyperresponsiveness: the need for a distinction between hypersensitivity and excessive airway narrowing

Sterk¹,

Bel²

1989

Eur Respir J

173

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Bronchial hyperresponsiveness is currently defined as an increase in sensitivity to a wide variety of airway narrowing stimuli. Most patients with asthma and chronic obstructive pulmonary disease (COPD) exhibit such an enhanced sensitivity. In asthma, in particular, this hypersensitivity is accompanied by excessive degrees of airway narrowing. This raises the question as to whether measures of sensitivity, e.g. the provocative concentration or dose producing 20% fall in FEV1 (PC20 or PD20), comprise all the relevant information in bronchial hyperresponsiveness. In adjunct to model studies, there is experimental evidence in man that the potential mechanisms of bronchial hyperresponsiveness can be divided into those causing hypersensitivity and those responsible for the increase in the maximal attainable degree of airway narrowing. The recognition and distinction of these components of hyperresponsiveness have clinical implications in the diagnosis and therapy of asthma and COPD. Bronchial hyperresponsiveness is a composite functional disorder, which requires treatment of each of its components.

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Section: Hypersensitivity: Shift Of the Dose-response Curvesupporting

confidence: 68%

Section: Shape Of Dose-response Curvesmentioning

confidence: 99%

Section: Shape Of Dose-response Curvesmentioning

confidence: 99%

Section: Shape Of Dose-response Curvesmentioning

confidence: 99%

Section: Excessive Airway Narrowing: Lift Of the Maximal Responsementioning

confidence: 99%

See 3 more Smart Citations

Bronchial hyperresponsiveness: the need for a distinction between hypersensitivity and excessive airway narrowing

Sterk¹,

Bel²

1989

Eur Respir J

173

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A Neuroendocrine Study of Supersensitivity in Tardive Dyskinesia

Tamminga¹

1977

Arch Gen Psychiatry

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Comparison of functional responses of canine coronary artery and saphenous vein

Isshiki

Akatsuka

Saito

et al. 1988

Cardiovasc Drug Ther

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Functional responses of canine circumflex coronary arteries and saphenous veins before and after grafting surgery were assessed following physiologic and pharmacologic interventions. Developed tension of ringed segments of vessels was recorded isometrically. Dose-dependent responses to norepinephrine revealed significantly greater responses of saphenous veins than coronary arteries (maximal responses were 2.79 +/- 0.45 and 0.44 +/- 0.34 g, respectively; p less than 0.001). Sensitivity to norepinephrine [as evaluated by 50% effective dose (ED50) value] was 3.3 times greater in the saphenous veins (p less than 0.001). STA2, a synthetic thromboxane A2 analog (see Methods), produced similar contractions of both vessels [maximal responses were 2.13 +/- 0.37 g in saphenous vein and 1.64 +/- 0.85 g in coronary artery; p less than not significant (NS)], while sensitivity to STA2 of saphenous veins was 3.1 times greater than that of coronary arteries (p less than 0.001). In contrast to the foregoing responses, coronary arteries demonstrated significantly greater responses to potassium than saphenous veins (maximal responses were 2.16 +/- 0.71 g and 1.40 +/- 0.56 g, respectively; p less than 0.001). Moreover, coronary arteries revealed 1.6 times greater sensitivity than saphenous veins (p less than 0.001). When saphenous veins were transplanted into the femoral artery, the segments of the grafts (2 weeks or 3 months after surgery) revealed 4.0 and 1.7 times greater sensitivity (denervation supersensitivity) to norepinephrine and potassium than those of the control veins (p less than 0.01, respectively). Contractile tension response, however, decreased by at least 50% 3 months after surgery, most probably due to a thickened vessel wall and a reduced compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

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Postjunctional supersensitivity and subsensitivity of excitable tissues to drugs

Cited by 90 publications

References 80 publications

Bronchial hyperresponsiveness: the need for a distinction between hypersensitivity and excessive airway narrowing

Bronchial hyperresponsiveness: the need for a distinction between hypersensitivity and excessive airway narrowing

A Neuroendocrine Study of Supersensitivity in Tardive Dyskinesia

Comparison of functional responses of canine coronary artery and saphenous vein

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