The Role of Histamine Receptors in Asthma

1981 ◽  
Vol 60 (4) ◽  
pp. 363-370 ◽  
Author(s):  
Noemi M. Eiser ◽  
Jane Mills ◽  
P. D. Snashall ◽  
A. Guz
Keyword(s):  
Receptor Antagonist ◽  
Dose Response ◽  
Normal Subjects ◽  
Histamine Receptors ◽  
Significant Shift ◽  
H1 Receptor ◽  
H2 Receptor Antagonist ◽  
Response Curves ◽  
The Right ◽  
H1 Receptor Antagonist

1. Eighteen non-asthmatic and 18 asthmatic subjects underwent challenge with increasing doses of histamine from a dosimeter—nebulizer system. Half the subjects in each group were atopic and half non-atopic. Bronchial response was monitored with serial measurements of specific airways conductance (sGaw) and a dose-response curve was constructed for each challenge. In addition, the nine atopic asthmatic patients underwent antigen challenges with a similar technique. In each subject the challenges were repeated, on separate days, after intravenous injections of either sodium chloride solution (150 mmol/l: saline) placebo, chlorpheniramine (an H1-receptor antagonist), cimetidine (an H2-receptor antagonist) or after both antagonists together. Baseline bronchial tone was always comparable within subjects immediately before challenge. 2. Cimetidine had no significant effect on baseline sGaw in any group, whereas chlorpheniramine raised baseline sGaw in the asthmatic subjects. Placebo did not alter the mean dose-response curves for histamine or antigen. However, there was a small, but significant, shift of the curves to the right after cimetidine and a much larger shift to the right with chlorpheniramine, whether given alone or with cimetidine. The effect of the histamine antagonists on histamine and antigen responses was very similar and there was no difference in the pattern of response among normal subjects as compared with asthmatics or among atopic as compared with non-atopic subjects. 3. In conclusion, the same pattern of histamine receptors exists in the airways of asthmatic and normal subjects. Histamine-induced bronchoconstriction is mediated predominantly via the H1-receptors, with little, if any, contribution from the H2-receptors. Histamine appears to be an important mediator in the immediate allergic response in airways since this response is blocked by an H1-receptor antagonist.

Histamine Receptors in Normal Human Bronchi

1980 ◽  
Vol 58 (6) ◽  
pp. 537-544 ◽  
Author(s):  
Noemi M. Eiser ◽  
Jane Mills ◽  
K. D. McRae ◽  
P. D. Snashall ◽  
A. Guz
Keyword(s):  
Receptor Antagonist ◽  
Dose Response ◽  
Response Curve ◽  
Normal Subjects ◽  
Dose Response Curve ◽  
Significant Shift ◽  
H2 Receptor Antagonist ◽  
Anticholinergic Activity ◽  
H2 Receptor ◽  
The Right

1. Nine normal subjects inhaled increasing concentrations of histamine aerosol from an aerosol generator attached to a breath-actuated dosimeter. The responses were monitored by measuring specific airways-conductance in a body plethysmograph, and the results were expressed as cumulative log dose-response curves. On separate days, histamine challenges were repeated after intravenous injections of sodium chloride solution (placebo), or an H1-receptor antagonist chlorpheniramine, or an H2-receptor antagonist cimetidine, or H1- and H2-receptor antagonists together. The anticholinergic activity of chlorpheniramine was estimated by comparing the effect of chlorpheniramine and atropine on methacholine challenge. 2. In all subjects the response to histamine was reproducible. Analysis of the variance showed that placebo did not alter the histamine dose-response curve significantly. In contrast, chlorpheniramine produced a large shift in the histamine dose-response curve to the right and cimetidine produced a significant shift of this curve to the right only at the highest dose of histamine. A combination of cimetidine and chlorpheniramine produced a shift not significantly different from that seen with chlorpheniramine alone. Chlorpheniramine showed no significant anticholinergic activity in this study. 3. In the normal subjects histamine-induced bronchoconstriction appeared to be mediated predominantly by the H1-receptors. The H2-receptor contributed very little to this bronchoconstriction.

Histamine receptors in mesenteric circulation of the cat and rat.

1978 ◽  
Vol 234 (4) ◽  
pp. E370
Author(s):  
P H Guth ◽  
E Smith
Keyword(s):  
Receptor Antagonist ◽  
Histamine Receptors ◽  
H1 Receptor ◽  
H2 Receptor Antagonist ◽  
Mesenteric Circulation ◽  
Microscopy Technique ◽  
Electromagnetic Probe ◽  
The Right ◽  
H1 Receptor Antagonist

This study was designed to ascertain the types and functions of histamine receptors in the mesenteric circulation of the cat and rat. Superior mesenteric artery (SMA) flow was measured via an electromagnetic probe in the cat and intestinal submucosal arteriolar diameter by an image-splitting in vivo microscopy technique in the cat and rat. Histamine infusion into the SMA caused dose-dependent decreases in mesenteric vascular resistance. Mepyramine, an H1 receptor antagonist (H1A), inhibited this effect, displacing the histamine dose-response curve to the right. Metiamide, an H2 receptor antagonist (H2A), alone had no effect, but in the presence of H1A caused further displacement of the curve to the right. In both the cat and the rat, histamine superfusion dilated the submucosal arterioles. H1A attenuated this effect. H2A alone had no effect, but in the presence of H1A there was nearly complete inhibition of the histamine effect. In conclusion, both H1 and H2 histamine receptors, both subserving vasodilatation, are present in the mesenteric circulation and the H1 receptor effect predominates.

Histamine's effect on pulmonary vascular resistance and compliance at elevated tone

1989 ◽  
Vol 257 (2) ◽  
pp. H618-H625
Author(s):  
S. A. Barman ◽  
A. E. Taylor
Keyword(s):  
Blood Vessel ◽  
Receptor Antagonist ◽  
Vascular Tone ◽  
H1 Receptor ◽  
H2 Receptor Antagonist ◽  
Small Blood Vessel ◽  
H2 Receptor ◽  
Longitudinal Resistance ◽  
Middle Compartment ◽  
H1 Receptor Antagonist

Histamine's effect on the longitudinal resistance and compliance distribution in the canine pulmonary circulation was determined under control and elevated vascular tone using the thromboxane analogue U46619. The arterial-, venous-, and double-occlusion techniques were used in isolated blood-perfused dog lungs at both constant flow and constant pressure. Large and small blood vessel resistances and compliances were studied in lungs given the following treatments: 1) histamine; 2) histamine in lungs pretreated with the H1-receptor antagonist diphenhydramine, and 3) histamine in lungs pretreated with the H2-receptor antagonist cimetidine. The results of this study indicate that histamine constricts small and large veins through H1-receptor mediation at both normal and elevated vascular tone. When vascular tone was elevated, H2-receptor vasodilatation was also apparent in all blood vessel segments. Histamine decreased total, middle compartment, and large vessel vascular compliances by an H1-receptor effect. When vascular tone was elevated, histamine's H1-receptor-mediated vasoconstrictor effect on compliance vessels was less due to the presence of an H2-receptor-mediated vasodilatory system.

Histamine H1- and H2-receptor vasodilation of canine intestinal circulation.

1977 ◽  
Vol 233 (3) ◽  
pp. E219 ◽  
Author(s):  
W Pawlik ◽  
L L Tague ◽  
B L Tepperman ◽  
T A Miller ◽  
E D Jacobson
Keyword(s):  
Receptor Antagonist ◽  
Potent Inhibitor ◽  
H1 Receptor ◽  
H2 Receptor Antagonist ◽  
H2 Receptor ◽  
Vasodilator Response ◽  
H2 Receptors ◽  
Anesthetized Dogs ◽  
H1 Receptor Antagonist ◽  
Intestinal Circulation

Studies were conducted in anesthetized dogs to determine whether the mesenteric vasodilator response to histamine is mediated by H1 receptors alone or whether H2 receptors are also involved in the response. Evidence favoring a role for both receptors included: 1) the vasodilator response to histamine was inhibited by either the H1-receptor antagonist, tripelennamine, or the H2-receptor antagonist, metiamide; 2) both the H1 agonist, 2-methylhistamine, and the H2 agonist, 4-methylhistamine, induced dilator responses in the mesenteric circulation; and 3) two temporal patterns of vasodilation could be distinguished, namely a transient spike and subsequent fade of blood flow (seen with either the H1 agonist or with histamine after H2-receptor blockade) and a sustained and stable increase in flow (seen with either the H2 agonist or with histamine after H1 blockade). Metiamide appeared to be a potent inhibitor of the mesenteric vasodilator response to histamine at least equal to tripelennamine.

H1-receptor-mediated excitation and facilitation of the heat response by histamine in canine visceral polymodal receptors studied in vitro

1996 ◽  
Vol 76 (3) ◽  
pp. 1396-1404 ◽  
Author(s):  
H. Koda ◽  
M. Minagawa ◽  
L. Si-Hong ◽  
K. Mizumura ◽  
T. Kumazawa
Keyword(s):  
Receptor Antagonist ◽  
Discharge Rate ◽  
Facilitatory Effect ◽  
Receptor Subtype ◽  
H1 Receptor ◽  
H2 Receptor Antagonist ◽  
Histamine Concentration ◽  
Heat Response ◽  
H1 Receptor Antagonist

1. We examined excitation and the facilitatory effect on the heat responses induced by histamine in visceral polymodal receptors with the use of the canine testis-spermatic nerve preparation in vitro. 2. The proportion of units that showed excitation (> 10 impulses 1 min after application of histamine was initiated) increased roughly with higher concentrations of histamine: 7% at 1 microM, 26% at 10 microM, 79% at 100 microM, and 61% at 1,000 microM. The discharge rate also increased with the concentration. 3. Histamine (100 and 1,000 microM) responses > 0.5 imp/s were observed only in units with conduction velocities (CVs) of < or = 10 m/s, but not in those with CVs faster than 10 m/s. On average, histamine-induced discharges were significantly greater in units with CVs of < or = 10 m/s at all concentrations > or = 10 microM. Thus units studied in this experiment were empirically divided into slow-CV (< or = m/s) and fast-CV (> 10 m/s) groups. 4. Histamine significantly facilitated the heat responses of the slow-CV group from 10 microM, and also facilitated the fast-CV group from 100 microM. This sensitizing effect was observed irrespective of the precedent histamine-induced excitation. The magnitude of sensitization tended to increase with an increase in histamine concentration. 5. For studying the histamine receptor subtype involved in excitation and facilitation, we used D-chlorpheniramine maleate (5 microM) (an H1 receptor antagonist), famotidine (20 microM) (an H2 receptor antagonist), and thioperamide maleate (20 microM) (an H3 receptor antagonist). The magnitude of histamine-induced excitation of the slow-CV group was significantly suppressed by the H1 receptor antagonist but not by other antagonists. 6. The facilitatory effect of histamine on the heat response was also suppressed by the H1 receptor antagonist in both slow- and fast-CV groups. 7. These results strongly suggested that both excitation and facilitation of the heat response induced by histamine are mediated through the H1 receptor.

Effects of histamine and histamine antagonists on intestinal capillary permeability

1981 ◽  
Vol 240 (5) ◽  
pp. G381-G386 ◽  
Author(s):  
N. A. Mortillaro ◽  
D. N. Granger ◽  
P. R. Kvietys ◽  
G. Rutili ◽  
A. E. Taylor
Keyword(s):  
Receptor Antagonist ◽  
Plasma Proteins ◽  
Protein Concentration ◽  
H1 Receptor ◽  
Total Protein Concentration ◽  
H2 Receptor Antagonist ◽  
H2 Receptor ◽  
Permeability Changes ◽  
H1 Receptor Antagonist ◽  
Molecular Radius

Steady-state lymph flow, blood flow, and lymph and plasma total protein concentration were measured in an autoperfused cat ileum preparation during the continuous infusion of histamine at venous pressures of 0, 10, 20, and 30 mmHg. The capillary osmotic reflection coefficients for total proteins and each protein fraction were estimated. In addition, the ileum was pretreated with an H1-receptor antagonist (diphenhydramine) or with an H2-receptor antagonist (cimetidine). The results suggest that histamine selectively increases the ileal vascular permeability to plasma proteins of a molecular radius up to 96 A. The H1-receptor antagonist did not alter the histamine-induced permeability changes but did block the observed initial vasodilation. The H2-receptor antagonist significantly reduced the permeability changes associated with histamine while having only a slight effect on the initial vasodilation. It is concluded that the activation of H1-receptors is predominantly associated with the initial vasodilation, whereas the H2-receptors are predominantly associated with permeability.

Pulmonary vascular histamine receptors in newborn and young lambs

1980 ◽  
Vol 49 (3) ◽  
pp. 380-385 ◽  
Author(s):  
B. W. Goetzman ◽  
J. M. Milstein
Keyword(s):  
Receptor Antagonist ◽  
Systemic Blood Pressure ◽  
Base Line ◽  
H1 Receptor ◽  
H2 Receptor Antagonist ◽  
Systemic Blood ◽  
H2 Receptor ◽  
Pulmonary Vasoconstriction ◽  
Alveolar Hypoxia ◽  
H1 Receptor Antagonist

Histamine H1- and H2-receptor-mediated pulmonary vascular responses were evaluated in six newborn and three 4-wk-old lambs. Base-line pulmonary vascular resistance (PVR) was elevated via alveolar hypoxia. Changes in PVR were then determined over a range of 0.001-1.0 microgram/kg of histamine. Multiple phases of relaxation of PVR were observed in all lambs. Two distinct plateaus of relaxation occurred between 0.001 and 0.075 micrograms/kg of histamine. The response at the first and major plateau was abolished by the H1-receptor antagonist, diphenhydramine. The second and smaller relaxation appeared to be attenuated by the H2-receptor antagonist, metiamide. Qualitatively similar results were obtained in the older lambs. Larger doses of histamine, 0.1-1.0 microgram/kg, produced further, but variable decreases in PVR as well as changes in systemic blood pressure. Our findings in newborn lambs are in contrast to those in adults where less sensitive H1-receptors mediate pulmonary vasoconstriction.

Role of histamine H1- and H2-receptors in postprandial intestinal hyperemia

1982 ◽  
Vol 243 (4) ◽  
pp. G248-G252 ◽  
Author(s):  
C. C. Chou ◽  
H. Siregar
Keyword(s):  
Blood Flow ◽  
Receptor Antagonist ◽  
H1 Receptor ◽  
H2 Receptor Antagonist ◽  
Arterial Infusion ◽  
H2 Receptors ◽  
Before And After ◽  
Anesthetized Dogs ◽  
H1 Receptor Antagonist

Studies were conducted in anesthetized dogs to assess whether histamine H1- and/or H2-receptors play a role in post-prandial intestinal hyperemia. The vascular and metabolic responses of jejunal segments to intra-arterial infusion of histamine and luminal placement of food before and after administration of tripelennamine, an H1-receptor antagonist, metiamide, an H2-receptor antagonist, and the combination of both antagonists were compared. Administration of the antagonists had no effect of jejunal blood flow and intestinal oxygen uptake (VO2). Tripelennamine or metiamide alone attenuated while the combination of both blocked the histamine-induced increases in blood flow and VO2. Metamide alone had no effect on the food-induced increases in flow and VO2. Tripelennamine significantly attenuated the food-induced increase in flow and blocked the increase in VO2. A 30% increase in flow was reduced to 15% after tripelennamine. The effects of tripelennamine plus metiamide were statistically the same as those of tripelennamine alone. It is concluded that endogenous histamines may play a role in postprandial intestinal hyperemia, and the effect is primarily mediated by the H1-receptors.

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