The Effect of H1 and H2 Receptor Antagonists on Bronchial Dose—Response Curves to Histamine in Normal Subjects

The histamine H2-receptor on the human parietal cell has been characterized by using dose-response curves and the negative logarithm of the molar concentration of an antagonist (pA2) analyses of cimetidine antagonism of betazole, histamine, and impromidine stimulation in isolated human and rabbit gastric glands. To evaluate the in vitro results, betazole-stimulated gastric acid secretion with and without cimetidine was also studied in healthy subjects. In the in vivo model, individual dose-response curves were shifted to the right with increasing cimetidine concentrations, but this was counteracted by increasing betazole doses, indicating competitive, reversible antagonism. The pA2 values ranged from 6.1 to 6.3. In isolated human gastric glands, impromidine was shown to be eight times more potent than histamine, indicating higher receptor affinity, but the maximally stimulated aminopyrine accumulation was the same as for histamine, and the pA2 values for cimetidine antagonism did not differ significantly, i.e., 5.7 (histamine) and 6.1 (impromidine). In isolated rabbit gastric glands, cimetidine inhibited the histamine- and impromidine-stimulated response with pA2 values of 6.0 and 7.3, respectively. Impromidine was shown to be approximately 100 times more potent than in human gastric glands, whereas histamine had the same potency. This confirms the role of the histamine H2-receptor and suggests a difference between the species concerning receptor affinity.

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Decreases in Residual Volume after Inhaled Salbutamol in Normal Subjects: Effect on Partial Expiratory dose-Response Curves

Clinical Science ◽

10.1042/cs069061pa ◽

1985 ◽

Vol 69 (s12) ◽

pp. 61P-61P

Author(s):

W.O.C.M. Cookson

Keyword(s):

Dose Response ◽

Normal Subjects ◽

Residual Volume ◽

Response Curves ◽

Dose Response Curves ◽

Inhaled Salbutamol

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Methacholine dose-response curves in normal and asthmatic man: Effect of starting conductance and pharmacological antagonism

Clinical Science ◽

10.1042/cs0660665 ◽

1984 ◽

Vol 66 (6) ◽

pp. 665-673 ◽

Cited By ~ 11

Author(s):

K. F. Chung ◽

P. D. Snashall

Keyword(s):

Dose Response ◽

Normal Subjects ◽

Small Degree ◽

Response Curves ◽

Significant Difference ◽

Positive Linear Correlation ◽

Dose Response Curves ◽

Dose Dependent Increase ◽

Dose Dependent ◽

Different Doses

1. The bronchial response of 11 normal and ten stable asthmatic subjects to increasing concentrations of methacholine aerosol was assessed by serial measurements of specific airways conductance (scaw) in a body plethysmograph. 2. Cumulative log dose-response curves were constructed. The threshold provocative dose of methacholine needed to cause a 35% fall in starting sCaw (pD35) and the steepest slope of the response were measured from each curve. 3. On separate days subjects were premedicated with 0.9% NaCl solution (control) in duplicate, chlorpheniramine, salbutamol and atropine, the last-named at two different doses, one twice the other. 4. Asthmatic subjects had a lower mean PD35 and a lower mean slope than normal subjects. 5. Pretreatment with salbutamol resulted in a greater increase in sGaw than after atropine but caused a smaller increase in PD35 in both groups. There was a dose-dependent increase in PD3s after the two doses of atropine, but no significant difference in bronchodilatation between doses. Mean steepest slope approximately doubled in these three sets of challenges. 6. Chlorpheniramine caused a small degree of bronchodilatation and there was a non-significant increase in mean PD3s and in mean steepest slope in both normal and asthmatic groups. 7. There was a positive linear correlation between starting sGaw and steepest slope in each group of premedicated challenges, such that when

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Night-time or morning dosing with H2-receptor antagonists: studies on acid inhibition in normal subjects

Alimentary Pharmacology & Therapeutics ◽

10.1111/j.1365-2036.1992.tb00059.x ◽

2007 ◽

Vol 6 (3) ◽

pp. 381-387 ◽

Cited By ~ 4

Author(s):

N. PATEL ◽

U. WARD ◽

M. J. ROGERS ◽

J. N. PRIMROSE

Keyword(s):

Normal Subjects ◽

Acid Inhibition ◽

Receptor Antagonists ◽

Night Time ◽

H2 Receptor Antagonists ◽

H2 Receptor

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Variability of airway responses to inhaled histamine in normal subjects

Journal of Applied Physiology ◽

10.1152/jappl.1979.47.1.51 ◽

1979 ◽

Vol 47 (1) ◽

pp. 51-58 ◽

Cited By ~ 37

Author(s):

M. P. Habib ◽

P. D. Pare ◽

L. A. Engel

Keyword(s):

Dose Response ◽

Lung Volume ◽

Normal Population ◽

Normal Subjects ◽

Beta Blockade ◽

Forced Expiration ◽

Response Curves ◽

Double Blind ◽

Dose Response Curves ◽

Airway Responses

Dose-response curves to inhaled histamine were studied in 12 normal subjects. Pulmonary resistance (RL) and dynamic compliance (Cdyn) were measured during tidal breathing, and maximum expiratory flow rates, at an absolute lung volume corresponding to 40% of control vital capacity, were obtained during forced expiration from tidal end inspiration (Vmax40p) and from total lung capacity (Vmax40c). Threshold was defined as the histamine dose at which a departure from the range of normal measurements was observed. RL and Vmax40p indicated lowest threshold values, which varied by a factor of 32 and 38, respectively. There was no correlation between reactivity, which reflects the slope of the dose-response curve beyond the threshold dose, and threshold doses, nor between the initial RL (normalized for lung volume) and either threshold or reactivity. In eight subjects, restudied on two occasions after 10 mg propranolol or after saline, injected in a double-blind manner, there was no change in the dose-response curves. These results indicate that different indices of bronchoconstriction may yield different dose-response curves and hence different sensitivities. In addition, a wide variation of airway responses to inhaled histamine exists in the normal population and beta-blockade does not influence this variability.

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Duodenal and antral mucosal prostaglandin E2 synthesis in a study of normal subjects and all stages of duodenal ulcer disease treated by H2 receptor antagonists.

Gut ◽

10.1136/gut.30.2.161 ◽

1989 ◽

Vol 30 (2) ◽

pp. 161-165 ◽

Cited By ~ 10

Author(s):

S Pugh ◽

S E Williams ◽

M R Lewin ◽

M Ishaque ◽

T P Barton ◽

...

Keyword(s):

Duodenal Ulcer ◽

Prostaglandin E2 ◽

Normal Subjects ◽

Receptor Antagonists ◽

H2 Receptor Antagonists ◽

Duodenal Ulcer Disease ◽

H2 Receptor ◽

Ulcer Disease

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The Effect of Deep Inspiration on Methacholine Dose–response Curves in Normal Subjects

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/ajrccm.156.4.96-11082 ◽

1997 ◽

Vol 156 (4) ◽

pp. 1278-1281 ◽

Cited By ~ 56

Author(s):

B. J. MOORE ◽

L. M. VERBURGT ◽

G. G. KING ◽

P. D. PARÉ

Keyword(s):

Dose Response ◽

Normal Subjects ◽

Deep Inspiration ◽

Response Curves ◽

Dose Response Curves

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Dose-response Curves in the Fibrin Plate Assay Fibrinolytic Activity of Proteases

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647705 ◽

1974 ◽

Vol 32 (02/03) ◽

pp. 356-365 ◽

Cited By ~ 12

Author(s):

F Haverkate ◽

D. W Traas

Keyword(s):

Dose Response ◽

Fibrinolytic Activity ◽

Enzyme Concentration ◽

Response Curves ◽

Agar Gel ◽

Porcine Tissue ◽

Plate Assay ◽

Fibrin Plate ◽

Different Types ◽

Dose Response Curves

SummaryIn the fibrin plate assay different types of relationships between the dose of applied proteolytic enzyme and the response have been previously reported. This study was undertaken to determine whether a generally valid relationship might exist.Trypsin, chymotrypsin, papain, the plasminogen activator urokinase and all of the microbial proteases investigated, including brinase gave a linear relationship between the logarithm of the enzyme concentration and the diameter of the circular lysed zone. A similar linearity of dose-response curves has frequently been found by investigators who used enzyme plate assays with substrates different from fibrin incorporated in an agar gel. Consequently, it seems that this linearity of dose-response curves is generally valid for the fibrin plate assay as well as for other enzyme plate bioassays.Both human plasmin and porcine tissue activator of plasminogen showed deviations from linearity of semi-logarithmic dose-response curves in the fibrin plate assay.

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BIOASSAY OF THYROID HORMONE USING HYPOTHYROID TADPOLES

Acta Endocrinologica ◽

10.1530/acta.0.0410143 ◽

1962 ◽

Vol 41 (1) ◽

pp. 143-153 ◽

Cited By ~ 2

Author(s):

U. Henriques

Keyword(s):

Thyroid Hormone ◽

Dose Response ◽

Developmental Rate ◽

Response Curves ◽

Sodium Salts ◽

Dose Response Curves

ABSTRACT A bioassay of thyroid hormone has been developed using Xenopus larvae made hypothyroid by the administration of thiourea. Only tadpoles of uniform developmental rate were used. Thiourea was given just before the metamorphotic climax in concentrations that produced neoteni in an early metamorphotic stage. During maintained thiourea neotoni, 1-thyroxine and 1-triiodothyronine were added as sodium salts to the water for three days and at the end of one week the stage of metamorphosis produced was determined. In this way identical dose-response curves were obtained for the two compounds. No qualitative differences between their effects were noted except that triiodothyronine seemed more toxic than thyroxine in equivalent doses. Triiodothyronine was found to be 7–12 times as active as thyroxine.

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