Histamine is an organic compound involved in various physiological processes in horses, including immune response, gastric acid secretion, and neurotransmission. It is synthesized from the amino acid histidine and is stored in mast cells and basophils, which release histamine in response to allergens or tissue injury. In horses, histamine plays a role in allergic reactions and inflammatory responses, influencing conditions such as equine asthma and urticaria. The compound interacts with specific histamine receptors, which mediate its effects on target tissues. This page compiles peer-reviewed research studies and scholarly articles that explore the synthesis, function, and clinical implications of histamine in equine health.
Leid RW.The investigation of the mast cell-basophil products has progressed from studies directed solely at implicating histamine or serotonin in allergic diseases to molecular definitions of pathways to target cell activation and mediator release. In addition, within the last several years the detection and molecular characterization of the many other mediators of immediate hypersensitivity have begun. This area should continue to prove a fruitful arena in the future. Identification of the physiologic importance of these mediators in the heaves syndrome or other potential equine allergic syndromes ma...
Eyre P, Elmes PJ, Strickland S.Spirally cut digital arteries and veins were mounted isotonically in organ baths containing oxygenated Krebs' Q-Henseleit solution. Twelve arterial and 12 venous preparations all contracted dose dependently when epinephrine, norepinephrine, serotonin, or histamine were added to the bathing fluid. Addition of hydrocortisone or betamethasone alone did not cause contractions in any of the tissues tested. However, when hydrocortisone or betamethasone was added to vessel strips that were partially contracted (40% to 60% maximal) by epinephrine, norepinephrine, or serotonin, each vessel strip invari...
Hanna CJ, Eyre P.Horses suffer from a respiratory condition, similar to human allergic asthma, that is characterized by severe dyspnea, wheezing, coughing, and mucus production. Mediator substances released during the allergic reaction may contract airways and pulmonary vasculature. Nothing is known of the effects of autacoids and other vasoactive substances on equine pulmonary vessels. Therefore, spiral strips of equine pulmonary vein were prepared in vitro and the effects of histamine (H), 5-hydroxytryptamine (5HT), bradykinin (BK), carbachol (Carb), and phenylephrine (phen) were studied. The order of contra...
Chand N, Eyre P.Histamine, 2-methylhistamine (a specific H1-agonist), 5-HT, PGF2alpha, SRS-A, bradykinin (BK) and carbachol contract bronchial and tracheal smooth muscles of the horse. Isoprenaline, PGE1, E2, dimaprit and 4-methylhistamine (last two = specific H2-agonists) relaxed airways which were partially contracted to carbachol. Mepyramine (a specific H1-antagonist) selectively antagonized contractions to histamine. In the presence of mepyramine, histamine caused relaxation of airways partially contracted to carbachol. Metiamide and burimamide (specific H2-antagonists) specifically antagonized or reverse...
Chand N, Eyre P.Nonsteroidal anti-inflammatory drugs inhibit the biosynthesis of kinins and prostaglandins and stabilize leukocyte lysosomal membranes. Nonsteroidal anti-inflammatory drugs also weakly block the biosynthesis of histamine and serotonin, and pharmacologically antagonize kinins, prostaglandins and slow-reacting substance of anaphylaxis. Nonsteroidal anti-inflammatory drugs effectively control both cardiovascular and respiratory manifestations of hypersensitivity in cattle and horses. This, coupled with the contrasting lack of effectiveness of "antiamine" drugs, suggests that bio-amines such as hi...
Robinson NE, Scott JB, Dabney JM, Jones GA.Digital vascular pressures, blood flow, and vascular resistances were measured in 11 control ponies and in 8 animals (7 ponies and 1 horse) affected with laminitis created by feeding a high starch ration. Animals with laminitis had increased digital blood flow, increased arterial, small vein, and large vein pressures, and decreased vascular resistances. Comparison of digital lymph flow rates and protein concentrations in animals with laminitis and control animals revealed no differences. Digital vascular responses of the 2 groups to acetylcholine, epinephrine, histamine, or serotonin also did ...
Eyre P.Systemic anaphylaxis was induced in seven groups of ponies. Systemic hypotension, pulmonary hypotension, and apnea were observed in the control group. Suppression of anaphylaxis was achieved most efficiently with sodium meclofenamate followed by acetylsalicylic acid and diethylcarboamazine. Tripelennamine and methysergide reduced anaphylaxis minimally and burimamide not at all. The findings suggest that histamine and serotonin are of relatively low significance in equine anaphylaxis whereas kinins, prostaglandins and slow reacting substance may be more important.
Burka JF, Deline TR, Holroyde MC, Eyre P.Horses were sensitized to bovine plasma in Freund's complete adjuvant. Leukocytes, separated from venous blood, yielded histamine upon incubation with bovine plasma. Ioslated lung fragments incubated with bovine plasma liberated histamine and 5-HT, but not SRS-A. Pulmonary veins obtained from the same animals contracted to histamine, 5-HT and to antigen (Schultz-Dale reaction). Histamine and 5-HT probably contribute to immediate-type hypersensitivity in horses whereas the role of SRS-A is not proved.
The Journal of physiologySeptember 1, 1975
Volume 250, Issue 3 633-649 doi: 10.1113/jphysiol.1975.sp011074
Johnson KG.1. A technique for perfusion of skin has been used to investigate a possible neurochemical basis for the different patterns of sweating in domestic animals. Evaporative water loss was measured from excised trunk skin, ears or tails perfused with a nutrient Krebs solution, to which drugs were added as required. Perfused skin was observed to sweat in response to administration of sudorific drugs, and some features of the patterns of sweating were similar to those which could be induced by heating or by drugs in conscious animals. 2. In sheep and goat skin, injections of adrenaline, and to a less...
Robinson NE, Dabney JM, Weidner WJ, Jones GA, Scott JB.The digital circulation was isolated in 12 ponies under pentobarbital anesthesia. Blood flow was either controlled by a pump or measured under natural perfusion. The responses to rapid changes and stoppages of blood flow indicated no evidence of autoregulation or reactive hyperemia. Local administration of acetylcholine, histamine, and prostaglandins E1 and E2 decreased prevenous resistance, whereas epinephrine and serotonin caused prevenous constriction. Large doses of epinephrine and serotonin decreased venous caliber. The effects of prostaglandins A1 and F2alpha were variable. The equine di...
Robinson NE, Jones GA, Scott JB, Dabney JM.We measured the flow rate and protein concentration of lymph collected from a digital lymphatic in eight anesthetized ponies. Additionally, we recorded systemic arterial pressure (Part), and small vein pressure (Psv). Control lymph flow averaged 0.068 ml/min, and contained 3.11 g/100 ml of protein with albumin/globulin ratio of 0.75. Twenty-minute local intra-arterial infusion of acetylcholine (10 mug/min.) elevated Psv but did not increase lymph flow rate or protein concentration. A 60-min local intra-arterial infusion of histamine (10 mug/min) produced a marked sustained increase in Psv and ...
Eyre P, Lewis AJ.1. Histamine in small doses caused systemic depressor responses in horses, whereas greater doses caused biphasic effects. All doses of 5-hydroxytrypt-amine (5-HT) were pressor and all doses of bradykinin depressor. All three active substances raised pulmonary artery pressure and lowered central venous pressure. 5-HT reduced ventilation volume. Histamine caused brief apnoea followed by hyperpnoea only.2. Acute anaphylaxis in the horse was accompanied by a severe systemic arterial depressor response, a pressor response in the pulmonary artery and vena cava, and alternating phases of apnoea and d...
Fernandes NS, Rantilla CK.The problem of histamine metabolism has long been the subject of research. The excretion of histamine during pregnancy has been studied in cats, mice, hamsters, and many other animals, and also in human beings. However, few papers have been published on the levels of histamine in the blood of pregnant animals. In this paper the variation in blood histamine levels in pregnant mares from the first month of pregnancy until term is reported.
Cheville NF, Prasse K, van der Maaten M, Boothe AD.A newborn foal developed generalized cutaneous mastocytosis characterized by multiple elevated nodules of mast cells in skin and basophil hyperplasia in bone marrow. Skin lesions began as small aggregates of mast cells that progressively enlarged, ulcerated, and regressed spontaneously. Eosinophil infiltration, collagen necrosis, and fibroplasia were characteristic of advanced lesions. Many new lesions developed during the first month of life but numbers progressively diminished. Large numbers of mast cells were present in biopsies of lymph node, spleen and bone marrow. Discrete aggregates of ...
WEGELIUS O.The number of mast cells per area and volume have been counted in the pleura, pericardium and capsula hepatis of cattle and horse.
The capsula hepatis of cattle contains a 5—10 times larger number of mast cells than the other tissues. The pleura pulmonalis showed a content of mast cells which was only a fraction of that in the liver capsule. The high histamine content found by Riley and coworkers when analyzing ox pleura seem to indicate that histamine is liberated not only from the mast cells, but also from other elements of the tissues.
Derksen FJ, Scott JS, Slocombe RF, Robinson NE.We determined the effect of IV administered beta 2-adrenergic receptor agonist clenbuterol on pulmonary function and on the response to histamine in 12 healthy ponies. Measurements were made at base line and after saline solution or clenbuterol was administered IV at a dosage of 0.2, 0.8, or 1.6 micrograms/kg. The dosage of clenbuterol used in each study was unknown to the investigators until all the data had been analyzed. Intravenous administration of saline solution or clenbuterol did not alter base-line pulmonary function significantly. Aerosol histamine administration significantly decrea...
Sweeney CR, Tomasic M, Russell GE.The effect of inhaled nitric oxide on pulmonary mechanics was studied in normal standing horses with histamine-induced bronchoconstriction. The respiratory health status of 6 normal horses was established on the basis of history, clinical and bronchoalveolar lavage examination. Intrathoracic pressures were estimated using distal oesophageal pressures. Respiratory gas flows were measured using a heated pneumotachograph. Pulmonary mechanics variables were determined from these measurements on a breath by breath basis. Bronchoconstriction was induced by nebulizing a 0.75% w/v solution of histamin...
Smyth GB, Duran S, Ravis W, Clark CR.Histamine type II (H2) antagonists inhibit gastric acid secretion and are useful in treating gastric and duodenal ulcer disease. To provide some information on the pharmacokinetics of the H2 antagonist cimetidine, adult horses were given 3.3 mg/kg cimetidine intravenously (iv) or 3.3 and 10 mg/kg orally. Plasma cimetidine concentrations after 3.3 mg/kg orally were too low to measure. Following 3.3 mg/kg iv, cimetidine displayed two-compartment characteristics with a t1/2 of 0.083 +/- 0.039 h and t1/2 of 2.23 +/- 0.64 h. The total body clearance was 0.443 +/- 0.160 litre/h/kg and the mean resid...
Moss A, Leise B, Hackett E.Laminitis is a complex and debilitating disease of horses. Numerous predisposing factors contribute to laminitis development, however the exact pathogenesis remains undetermined. Serum T4, cortisol, and histamine are components of the innate stress response and could play a causative or contributory role. Stress hormone concentrations in laminitis are largely unknown. Objective: To evaluate parameters associated with stress response in horses with laminitis, and compare these to healthy horses and horses with gastrointestinal (GI) disease. Methods: Thirty-eight adult horses presenting for non-...
Martínez AC, Rivera L, Raposo R, García-Sacristán A, Benedito S.The effect of histamine (10(-9)-10(-3) M) on horse penile dorsal artery was evaluated. Precontracted vessels showed a biphasic response (relaxation-contraction) to histamine, while at basal tone, histamine only induced a contractile effect. The H1 receptor agonist, 2-pyridylethylamine (PEA) (10(-9)-10(-3) M), induced concentration-dependent relaxation in precontracted rings and provoked vasoconstriction at basal tone. Mepyramine (10(-9)-10(8) M), an H1 receptor antagonist, competitively antagonized the relaxant response to histamine (pA2 = 9.7) and PEA (pA2 = 9.2). At basal tone, mepyramine (1...
Weston MC, Collins ME, Cunningham FM.Inappropriately activated eosinophils can contribute to disease pathogenesis and intracellular signalling pathways that regulate functional responses may represent a therapeutic target. Little is known about intracellular signalling in equine eosinophils and this study examined the role of phospholipase C (PLC) and a range of protein kinases on responses to histamine and CCL11. Histamine (10(-4) M) or CCL11 (5.6 x 10(-9) M)-induced actin polymerization, migration and superoxide production by eosinophils from healthy horses were compared in the presence and absence of selective kinase inhibitor...
Bello TR.Antiparasitic efficacy of ivermectin against migrating Gasterophilus intestinalis was evaluated in 36 treated and 24 nontreated (n = 12) or vehicle-treated (n = 12) ponies experimentally and naturally infected with G intestinalis and naturally infected with G nasalis. Each pony was experimentally infected with 500 G intestinalis 1st instars in 2 divided doses on days -14 and -7 before treatment. On day 0, ivermectin was administered at the rate of 200 micrograms/kg of body weight by IV (n = 12) or IM injection (n = 12) or given as an oral paste (n = 12). Ponies were euthanatized and necropsied...
Campbell-Thompson M.Equine oxyntic mucosal cells were obtained by sequential exposure to pronase and collagenase. Acid production by parietal cells was assessed by uptake of [14C]aminopyrine (AP), a weak base that accumulates in intracellular acidic spaces. Incubation for various times revealed a maximal AP uptake at 10 minutes for histamine and carbachol. Similar secretagogue responses were observed for parietal cells from the mucosal cell preparation or after enrichment by elutriation. Histamine and isobutyl-methylxanthine (IBMX) stimulated AP uptake with a dose-dependent response and maximal effective concentr...
Petersen A, Schott HC.To determine whether dexamethasone or hydroxyzine affect intradermal testing (IDT) and allergen-specific IgE serum testing (ASIST) results in horses, these tests were performed serially in five horses without signs of atopic dermatitis before and after treatment with the drugs. IDT consisted of saline, histamine (1:100,000 w/v) and eight commercial extracts; results were evaluated as subjective scores by comparison to saline (0) and histamine (4) and as objective measurement of wheal diameter (mm). After baseline testing, dexamethasone (20 mg) was administered intramuscularly daily for 7 days....
Robinson NE, Jones GA, Scott JB, Dabney JM.We measured the flow rate and protein concentration of lymph collected from a digital lymphatic in eight anesthetized ponies. Additionally, we recorded systemic arterial pressure (Part), and small vein pressure (Psv). Control lymph flow averaged 0.068 ml/min, and contained 3.11 g/100 ml of protein with albumin/globulin ratio of 0.75. Twenty-minute local intra-arterial infusion of acetylcholine (10 mug/min.) elevated Psv but did not increase lymph flow rate or protein concentration. A 60-min local intra-arterial infusion of histamine (10 mug/min) produced a marked sustained increase in Psv and ...
Sangiah S, McAllister CC, Amouzadeh HR.The basal gastric pH, free and total acid contents from five adult horses were determined at two-hour intervals for six- to eight-hour periods. The basal gastric pH, free and total acid contents varied from 2.14 +/- 0.08 to 2.41 +/- 0.14, 28.63 +/- 8.27 to 17.89 +/- 2.86 mmol litre-1 and 41.38 +/- 9.72 to 37.38 +/- 3.70 mmol litre-1, respectively. Cimetidine (8.8 mg kg-1 orally) and ranitidine (2.2 mg kg-1 orally) increased the basal gastric pH to above 3.6 (P less than 0.05) with a concomitant reduction of 75 per cent and 75 to 100 per cent in the basal gastric free acid content, respectively...
Scott JS, Berney CE, Derksen FJ, Robinson NE.Pulmonary function measurements were made in control ponies and in ponies with recurrent obstructive pulmonary disease (principals) during clinical remission and during an attack of acute airway obstruction. The ponies were given beta-adrenergic antagonists and agonists to determine the role of beta receptors in recurrent obstructive pulmonary disease, and to determine the subtypes of beta receptors mediating bronchodilation in ponies. Aerosol administration of the beta antagonists, propranolol (beta 1 and beta 2), atenolol (beta 1), and butoxamine (beta 2) decreased dynamic compliance (Cdyn) ...
Wolter R, Durix A, Letourneau JC, Carcelen M, Henry N.One pony has been subjected to the intravenous injections of L-lactic acid. Two other ponies have been trained to intracaecal administration of L-lactic acid or sucrose. The obtained results show that: Intravenous injection of lactic acid increases the concentration of histamin and lactic acid, decreases the level of magnesium and reduces the pressure of carbon dioxide in the blood (the control animals and the treated animals) without the clinical symptoms of lactic acidosis. Intracaecal administration of lactic acid induces a high liberation of histamin in the caecum (the control animals and ...
Greenaway EC, Sepulveda MF, Cunningham FM, Goode NT.Eosinophils have been implicated in the pathogenesis of the seasonal equine allergic skin disease, sweet itch. Protein kinase C (PKC) is involved in regulating eosinophil function and antigen challenge has been reported to alter PKC isotype expression in blood eosinophils from allergic human subjects. Here we have compared the pattern of PKC isotype expression in eosinophils from sweet itch ponies with that in cells from normal ponies both during the active and inactive phases of the disease. A role for PKC in histamine-induced eosinophil activation was also investigated. Conventional PKCs alp...
Aguilera-Tejéro E, Pascoe JR, Woliner MJ.Effects of phenylbutazone (PBZ) and furosemide (FUR) on the respiratory tract of horses were evaluated, focusing on bronchial responsiveness. Four healthy Thoroughbreds were used and data were analyzed by use of a Latin square design. Histamine provocation tests (0.5, 1, 2, and 4 micrograms/min, i.v.) were done: (1) without prior treatment with PBZ or FUR, (2) 30 minutes after administration of PBZ (8 mg/kg, i.v.), (3) 1 hour after administration of FUR (1 mg/kg, i.v.), and (4) after administration of PBZ plus FUR. Pulmonary function tests (dynamic compliance, resistance, respiratory frequency...
Lewis N, Racklyeft DJ.The clinical course of toxic envenomation of a mare and her foal after an attack by a swarm of bees in the Upper Hunter Valley of New South Wales is described. Early agitation and urticaria were followed by more severe systemic clinical signs within 18 h. There was severe, generalised angioedema, rhabdomyolysis, hypovolaemia, gastrointestinal stasis and renal injury. A particular feature in the mare was almost maniacal behaviour during the first 48 h. Clinical pathological examination showed evidence of haemoconcentration, intravascular haemolysis, thrombocytopenia, azotaemia, rhabdomyolysis a...
Olson LE, Perkowski SZ, Mason DE, Muir WW.Strips of trachealis muscle were dissected from the midcervical portion of the trachea of horses that were free of respiratory tract disease, and the overlying epithelium and mucosa were removed. Muscle strips were suspended in tissue baths that were filled with Krebs-bicarbonate solution, aerated with 5% CO2 in oxygen and maintained at 37 C. Isometric tension was continuously recorded. The increase in active isometric tension was concentration dependent when acetylcholine (10(-9) to 10(-4) M) or histamine (10(-9) to 10(-4) M) was added to the tissue baths in 0.5-logarithmic increments. When t...
Murray MJ, Eichorn ES.To determine the effect of decreasing gastric acidity in a feed-deprivation protocol on induction of gastric ulcers, and to determine whether stall confinement may be a factor contributing to gastric ulceration in horses. Methods: 8 adult horses, 4 geldings and 4 mares, 3 to 8 years old, and 7 adult horses, 5 geldings and 2 mares, 4 to 11 years old. Methods: Gastric ulceration was induced in horses by alternating 24-hour periods of feed deprivation and ad libitum access to hay, for a total of 96 hours' feed deprivation. This protocol was repeated with the horses receiving the histamine type-2 ...
Chen H, Wang L, Zeller M, Hornshaw M, Wu Y, Zhou M, Li J, Hang X, Cai J, Chen T, Shaw C.From defensive skin secretions acquired from two species of African hyperoliid frogs, Kassina maculata and Kassina senegalensis, we have isolated two structurally related, C-terminally amidated tridecapeptides of novel primary structure that exhibit a broad spectrum of biological activity. In reflection of their structural novelty and species of origin, we named the peptides kassorin M (FLEGLLNTVTGLLamide; 1387.8 Da) and kassorin S (FLGGILNTITGLLamide; 1329.8 Da), respectively. The primary structure and organisation of the biosynthetic precursors of kassorins M and S were deduced from cloned s...
Scott JS, Broadstone RV, Derksen FJ, Robinson NE.Ponies with recurrent airway obstruction have hyperresponsive airways during acute disease exacerbations but not during clinical remission. We examined the effect of beta-adrenergic blockade with propranolol on airway responsiveness to aerosol histamine in six ponies with recurrent airway obstruction and six age- and gender-matched controls. Measurements were made with principal ponies in clinical remission (period A) and during an acute period of airway obstruction (period B). beta-Adrenergic blockade did not change airway responsiveness, dynamic compliance (Cdyn), or pulmonary resistance (RL...
Hare JE, Viel L, Conlon PD, Marshall JS.Pulmonary mast cells (PMC) are important components of the inflammatory process in equine allergic lung diseases such as heaves. Very little, however, is known of the degranulation kinetics of these cells and thus, their pathophysiologic role remains largely speculative. The purpose of this study was to develop a repeatable protocol for in vitro equine PMC degranulation. Five mature horses (sex: 2 M, 3 F; age: 8.8 +/- 6.5 y), historically free of pulmonary disease and normal on clinical respiratory examination, arterial blood gas analysis, pulmonary mechanics testing and histamine inhalation c...
Stammwitz V, Honnens Ä, Hochhuth D, Schuberth HJ.Between 2015 and 2017, a marked increase of anaphylactic-like reactions after intravenous administration of gentamicin was observed first in horses and, later, also in humans. This worldwide issue led to safety measures including product recalls and safety warnings. Here, a German Marketing Authorization Holder (MAH) of an early and intensely affected veterinary product containing gentamicin describes the clinical approach of the company to analyze the root cause and identify the causative agent in the active pharmaceutical ingredient (API). The pharmacovigilance data of the MAH are presented,...
Pessoa VC, Branco-Ferreira M, Jónsdóttir S, Marti E, Tilley P.Thirty controls (C) and 30 IBH-affected (T) Lusitano horses were evaluated. T horses were included based on anamnesis and physical examination, supported by questionnaires. All horses were submitted to skin tests, Intrademal (IDT) and Skin Prick Tests (SPT), on the neck with 14 specific allergens, 13 recombinant proteins (r-proteins) from Culicoides nubeculosus (Cul n) and Culicoides obsoletus (Cul o) salivary glands and Culicoides nubeculosus Whole Body Extract (Cul n WBE). Addicionally, a cluster of six T and six C horses were also tested with Cul n 3 and Cul n 4 produced in insect cells and...
Robins TJ, Bedenice D, Mazan M.(1) Background: Equine asthma (EA) is a pervasive and important cause of poor performance and respiratory morbidity in horses. Diagnosis of EA includes an owner complaint, clinical scoring, lung function testing, and cytological analysis of bronchoalveolar lavage (BAL) cytology. There is a paucity of information about the longitudinal course of the disease using these outcome assessments; thus, this study sought to describe and quantify, in horses with more than one visit to a specialty pulmonary clinic in New England, the type and range of clinical presentations with an eventual diagnosis of ...
