Piperonyl-ranitidine: An H2-antagonist able to interact with cholinergic M3-muscarine receptors

AbstractHistamine is a monoamine synthesized from the amino acid histidine that is well-known for its role in IgE-mediated anaphylaxis but has shown pleiotropic effects on the immune system, especially in order to promote inflammatory responses. H1-receptor antagonist are common drugs used in mild/moderate allergic reactions whereas H2-receptor antagonist are commonly administered in gastric ulcer but showed some properties in allergy too. The EAACI guidelines for diagnosis and treatment of anaphylactic reactions recommend their use as third-line therapy in adjunct to H1-antagonists. The purpose of this article is to produce a complete summary of findings and evidence known so far about the usefulness of H2-receptor antagonist in allergic reactons.

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Effects of toxic doses of a novel histamine (H2) antagonist on the rat thyroid gland

Food and Chemical Toxicology ◽

10.1016/0278-6915(87)90235-3 ◽

1987 ◽

Vol 25 (10) ◽

pp. 787-794 ◽

Cited By ~ 18

Author(s):

C.G. Brown ◽

R.F. Harland ◽

I.R. Major ◽

C.K. Atterwill

Keyword(s):

Thyroid Gland ◽

H2 Antagonist ◽

Histamine H2 Antagonist ◽

Rat Thyroid ◽

Rat Thyroid Gland

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H2-antagonist/alcohol interaction only minor

Reactions Weekly ◽

10.2165/00128415-199405030-00003 ◽

1994 ◽

Vol &NA; (503) ◽

pp. 2

Author(s):

&NA;

Keyword(s):

Alcohol Interaction ◽

H2 Antagonist

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Conservative and nonconservative inhibitors of gastric acid secretion

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1987.253.3.g359 ◽

1987 ◽

Vol 253 (3) ◽

pp. G359-G368 ◽

Cited By ~ 1

Author(s):

E. B. Ekblad ◽

V. Licko

Keyword(s):

Steady State ◽

Acid Secretion ◽

Initial Step ◽

No Net Loss ◽

Apparent Loss ◽

H2 Antagonist ◽

Flow Through ◽

Ph Stat ◽

High Concentrations ◽

Continuous Presence

Inhibitors of the initial step (H2-antagonist) and of the final step (thiocyanate, SCN-; and nitrite, NO2-) were used to study the dynamics of acid secretion in isolated frog gastric mucosa. Tissues were mounted in flow-through chambers, and the acid secretion rate (SR) was recorded on a pH-stat microprocessor. Continuous presence of H2-antagonist decreases the SR to a lower steady state, and on removal the SR returns to basal SR, causing a net loss of acid, the nonconservative effect. The amount of lost acid is a unique function of exposure, thus, independent of the patterns (pulses or steps) of inhibition. In contrast, continuous presence of SCN- or NO2- (below 3 mM) results in an undershoot in SR with a return to basal SR, whereas at higher concentrations there is no return. Removal of these inhibitors causes an overshoot in SR with return to basal SR. The rebound acid is equal to acid suppressed by NO2- and low concentration of SCN-, resulting in no net loss of acid, the conservative effect, whereas at high concentrations of SCN- there is an apparent loss of acid. In maximally secreting tissue the overshoot of SR is not observed. However, the acid is not lost, merely delayed. In resting tissue NO2- also merely delays the exit of the acid produced in response to forskolin. The rebound acid is proposed to reside in a sequestered "acid" pool that is stable for at least 120 min. Results with NO2- and SCN- suggest an effect on a saturable exit enzyme, possibly the K+-H+-ATPase.

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Histamine augments colonic secretion in guinea pig distal colon

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1990.258.3.g432 ◽

1990 ◽

Vol 258 (3) ◽

pp. G432-G439 ◽

Cited By ~ 7

Author(s):

Y. Z. Wang ◽

H. J. Cooke ◽

H. C. Su ◽

R. Fertel

Keyword(s):

Short Circuit ◽

Nordihydroguaiaretic Acid ◽

Short Circuit Current ◽

Intestinal Secretion ◽

Distal Colon ◽

H2 Antagonist ◽

Colonic Secretion ◽

Set Up ◽

Colonic Transport

We tested the hypothesis that the role of histamine in the control of intestinal secretion is mediated by prostaglandins (PGs). The effects of histamine on ion transport were examined in muscle-stripped sheets of mucosa/submucosa set up in flux chambers. Histamine evoked a transient concentration-dependent increase in short-circuit current (Isc) that was reduced by the Cl- transport inhibitor bumetanide. Histamine also caused the release of PGE2. The Isc response to histamine was reduced by indomethacin and piroxicam, which block PG formation, but not by nordihydroguaiaretic acid, which prevents production of lipoxygenase products. 2-Methylhistamine, but not dimaprit, evoked a concentration-dependent increase in Isc. The Isc response to histamine was reduced by the H1-blocker pyrilamine, but not by the H2-antagonist cimetidine. In addition to its direct effect, histamine augmented the responses of endogenously released neurotransmitters with and without indomethacin and hexamethonium. Tetrodotoxin (TTX) reduced the Isc response to 10(-3) M histamine. In the presence of TTX, exogenous histamine amplified the responses to PGs, vasoactive intestinal polypeptide, 2-chloroadenosine, bethanechol, and carbachol. These results suggest that histamine acts at H1-receptors on cells within the gut to mediate intestinal Cl- secretion in part by releasing PGs and by augmenting the actions of endogenously released neurotransmitters. Our results indicate that histamine has a role in the regulation of colonic transport function.

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SUBTYPES OF MUSCARINE RECEPTORS IN THE GUINEA-PIG ILEUM

Receptors and Centrally Acting Drugs Pharmacokinetics and Drug Metabolism ◽

10.1016/b978-0-08-034191-0.50007-6 ◽

1986 ◽

pp. 19-22

Author(s):

H. KILBINGER

Keyword(s):

Guinea Pig ◽

Guinea Pig Ileum ◽

Muscarine Receptors

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Effect of histamine on microvascular permeability in the rat stomach

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1983.245.2.g201 ◽

1983 ◽

Vol 245 (2) ◽

pp. G201-G207

Author(s):

H. Nagata ◽

P. H. Guth

Keyword(s):

Histamine Receptors ◽

Microvascular Permeability ◽

In Vivo Microscopy ◽

Rat Stomach ◽

Serosal Surface ◽

H2 Antagonist ◽

H1 Antagonist ◽

Dose Dependent ◽

Muscularis Externa

The effect of histamine on gastric microvascular permeability to macromolecules in the rat was studied using fluorescent in vivo microscopy. Histamine was applied topically to the serosal surface for study of the muscularis externa, to the submucosa, and to the superficial mucosa, and the area of leaks of a fluorescein-albumin conjugate from microvessels was quantitated. In the muscularis externa both histamine and an H1-agonist, but not an H2-agonist, caused dose-dependent leak of conjugate from venules. An H1-antagonist, but not an H2-antagonist, decreased the histamine-induced leak. In the submucosa histamine caused dose-dependent dilatation of arterioles but not leak of conjugate. In contrast, bradykinin caused both dose-dependent dilatation of arterioles and leak of conjugate from venules. In the superficial mucosa histamine did not cause any leak. In conclusion, topical histamine 1) increased microvascular permeability to macromolecules from venules in the muscularis externa via H1-receptors, 2) did not affect microvascular permeability in the submucosa (this may be due to lack of histamine receptors on the venules as bradykinin increased venular permeability), and 3) did not affect microvascular permeability in the superficial mucosa, but there might not have been adequate histamine backdiffusion.

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