Biomaterial Database

Functional depression of H2 histamine receptors in sheep with experimental allergic asthma. 1983

T Ahmed, and J P Krainson, and L D Yerger

We tested the hypothesis that airway hyperresponsiveness to histamine in the allergic sheep is related to functional depression of H2 histamine receptors. Thirteen of 32 sheep responded with bronchoconstriction to inhaled Ascaris suum antigen (allergic sheep), and the remainder served as controls (nonallergic sheep). In the allergic sheep, 50 and 100 breaths of 5% histamine solution increased mean pulmonary resistance (RL) to 235% and 438% of baselines, respectively. The corresponding values in nonallergic sheep were 200% and 211%, indicating a greater response to the higher dose of histamine in allergic sheep. Selective H1-receptor stimulation with 50 breaths of histamine (pretreatment with the H2-receptor antagonist metiamide) failed to enhance the effect of histamine in allergic sheep (mean RL increased to 239% of baseline) whereas it enhanced the histamine response in nonallergic sheep (RL increased to 438% of baseline). Selective H2-receptor stimulation (pretreatment with the H1-receptor antagonist chlorpheniramine) caused histamine to decrease RL by 31% in the nonallergic sheep group; it blocked but did not reverse the histamine effect in the allergic sheep. Similar observations were made in a different group of animals when selective H1- or selective H2-receptor stimulation was produced by 100 breaths of histamine. The cutaneous wheal response to intradermal histamine dilutions of 0.0001. 0.001, 0.01, and 1 mg/ml was similar in both groups. In nonallergic sheep, both chlorpheniramine and metiamide blunted the cutaneous wheal response. In allergic animals, only chlorpheniramine blunted the cutaneous wheal response, whereas metiamide was without effect. We conclude that airway hyperresponsiveness to histamine in allergic sheep is related to a functional depression of H2 receptors and that such a defect is observed both in the airways as well as in the skin.

UI	MeSH Term	Description	Entries
D011968	Receptors, Histamine	Cell-surface proteins that bind histamine and trigger intracellular changes influencing the behavior of cells. Histamine receptors are widespread in the central nervous system and in peripheral tissues. Three types have been recognized and designated H1, H2, and H3. They differ in pharmacology, distribution, and mode of action.	Histamine Binding Sites,Histamine Receptors,Histamine Receptor,Binding Sites, Histamine,Receptor, Histamine,Sites, Histamine Binding
D011970	Receptors, Histamine H2	A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H2 receptors act via G-proteins to stimulate ADENYLYL CYCLASES. Among the many responses mediated by these receptors are gastric acid secretion, smooth muscle relaxation, inotropic and chronotropic effects on heart muscle, and inhibition of lymphocyte function. (From Biochem Soc Trans 1992 Feb;20(1):122-5)	Histamine H2 Receptors,H2 Receptors,Receptors, H2,H2 Receptors, Histamine
D002744	Chlorpheniramine	A histamine H1 antagonist used in allergic reactions, hay fever, rhinitis, urticaria, and asthma. It has also been used in veterinary applications. One of the most widely used of the classical antihistaminics, it generally causes less drowsiness and sedation than PROMETHAZINE.	Chlorphenamine,Chlorprophenpyridamine,Aller-Chlor,Antihistaminico Llorens,Chlo-Amine,Chlor-100,Chlor-Trimeton,Chlor-Tripolon,Chlorpheniramine Maleate,Chlorpheniramine Tannate,Chlorpro,Chlorspan 12,Chlortab-4,Cloro-Trimeton,Efidac 24,Kloromin,Piriton,Teldrin,Maleate, Chlorpheniramine,Tannate, Chlorpheniramine
D005260	Female		Females
D006632	Histamine	An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.	Ceplene,Histamine Dihydrochloride,Histamine Hydrochloride,Peremin
D006634	Histamine H1 Antagonists	Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.	Antihistamines, Classical,Antihistaminics, Classical,Antihistaminics, H1,Histamine H1 Antagonist,Histamine H1 Receptor Antagonist,Histamine H1 Receptor Antagonists,Histamine H1 Receptor Blockaders,Antagonists, Histamine H1,Antagonists, Histamine H1 Receptor,Antihistamines, Sedating,Blockaders, Histamine H1 Receptor,First Generation H1 Antagonists,H1 Receptor Blockaders,Histamine H1 Blockers,Receptor Blockaders, H1,Antagonist, Histamine H1,Classical Antihistamines,Classical Antihistaminics,H1 Antagonist, Histamine,H1 Antagonists, Histamine,H1 Antihistaminics,Sedating Antihistamines
D006635	Histamine H2 Antagonists	Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood.	Antihistaminics, H2,H2 Receptor Blockader,Histamine H2 Antagonist,Histamine H2 Blocker,Histamine H2 Receptor Antagonist,Histamine H2 Receptor Antagonists,Histamine H2 Receptor Blockader,Histamine H2 Receptor Blockaders,Antagonists, Histamine H2,Blockaders, Histamine H2 Receptor,H2 Receptor Blockaders,Histamine H2 Blockers,Receptor Antagonists, Histamine H2,Receptor Blockaders, H2,Antagonist, Histamine H2,Blockader, H2 Receptor,Blockaders, H2 Receptor,Blocker, Histamine H2,Blockers, Histamine H2,H2 Antagonist, Histamine,H2 Antagonists, Histamine,H2 Antihistaminics,H2 Blocker, Histamine,H2 Blockers, Histamine,Receptor Blockader, H2
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001249	Asthma	A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).	Asthma, Bronchial,Bronchial Asthma,Asthmas
D012756	Sheep	Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.	Ovis,Sheep, Dall,Dall Sheep,Ovis dalli