Histamine H2 receptor mediated relaxation of hamster (Mesocricetus auratus) uterus.

Histamine and 4-methyl histamine produced relaxation of KCl depolarized hamster uterus in vitro. The relaxation was selectively antagonized by histamine H2 receptor antagonist cimetidine which failed to antagonize the isoprenaline induced relaxation. The histamine induced relaxation was, further, not mediated through catecholamine release. The study indicated that, as in the albino rat, histamine produces relaxation of the hamster uterus mediated via the H2 receptors.

Effects of a histamine type-2 receptor antagonist (BMY-25368) on gastric secretion in horses.

The effects of a potent new histamine-2 (H2) receptor antagonist, BMY-25368, were studied on gastric acid secretion in 5 foals from which food was withheld. Doses of 0.02, 0.11, 0.22, and 1.10 mg/kg of body weight were administered IM in a randomly assigned treatment sequence. Following BMY-25368 administration, hydrogen ion concentration was decreased and mean pH was higher than baseline values in a dose-response pattern. At the 0.22 and 1.10 mg/kg doses, the high pH was sustained for greater than 4 hours. The BMY-25368 thus may be useful for treating gastric ulcer disease in horses.

The role of histamine in cardiac anaphylaxis; characterization of histaminergic H1- and H2-receptor effects.

Histamine is known to act as a direct stimulator. In the heart, two types of histamine receptors are present: H1- and H2-receptors. H2-receptors cause an increase in heart rate and contractility as well as coronary vasodilatation, whereas H1-receptors mediate chronotropic effects and coronary vasoconstriction. During anaphylactic states, histamine is released from cardiac tissue where it is stored in large amounts. The present study was designed to ascertain the role of cardiac histamine release during cardiac anaphylaxis. In guinea pigs, sensitization was produced by intraperitoneal administration of ovalbumin (O). 14 days after sensitization, the effects of an intracoronary infusion of O (1.1 x 10(-8) moles/min) were tested in the isolated perfused heart preparation. The response of the sensitized hearts to O was characterized by a rapid increase in contractile force (dp/dtmax 120% above baseline after 30 s), followed by a decrease reaching a minimum of 30% below baseline after 10 min. Over the same time range, the heart rate first increased (+24%), then decreased, concurrent with the appearance of arrhythmias, before reaching baseline level. Coronary flow decreased (-40% after 1 min) and finally stabilized at a new steady state (-20% below baseline). It is concluded that histamine might be an important mediator of these effects, since in the presence of H2-receptor blockade with cimetidine (6.2 x 10(-7) moles/min), the positive inotropic and chronotropic effects were completely antagonized. Furthermore, a decrease in heart rate and contractility occurred (-25% and -50% after 2 min, respectively). Finally, coronary constriction was intensified and resulted in coronary spasm with flow rates approaching zero after 1 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacological profile of new histamine H2-receptor antagonists related to cimetidine, ranitidine and lamtidine.

New compounds structurally related to cimetidine, ranitidine and lamtidine have been prepared and tested for their histamine H2-receptor blocking activity on guinea-pig atria, rat perfused stomach and frog isolated gastric mucosa. These derivatives contain as a polar group, a diaminofurazan moiety, a 3-amino-4-methylfurazan or a 3-amino-4-phenylfurazan moiety. Ranitidine and lamtidine analogues display strong H2-antagonist activity in-vitro (KB on atria 0.037 microM and 0.0039 microM, respectively) and in-vivo on the lumen-perfused stomach of the anaesthetized rat (ID50 0.13 mumol kg-1 and 0.023 mumol kg-1 i.v., respectively). However, lamtidine analogues are ineffective in blocking the histamine-induced increase of H+ output in the frog isolated gastric mucosa. On the basis of the anomalous results in the frog, it is concluded that caution must be exercised in extrapolating information from amphibian to mammalian tissues with regard to the structure and the function of histamine receptors.

Histamine H1, H2 receptor effects on mechanics of ventilation and gas exchange in neonatal calves.

The effect of histamine infusion (IV) on pulmonary mechanical and gas exchange properties of healthy neonatal Holstein-Friesian calves was determined. Histamine increased pulmonary resistance and static pressure-volume hysteresis and decreased dynamic compliance, but failed to change static compliance; changes were compatible with constriction of both large and small airways without a change in lung elasticity. Histamine decreased arterial oxygen tension by increasing the alveolar-arterial oxygen difference, probably because ventilation-perfusion inequalities resulted from small airway constriction. The pulmonary mechanical and gas exchange effects of histamine were prevented by pretreatment with the H1 receptor antagonist, tripelennamine, but not with the H2 receptor antagonist, metiamide. The histamine-induced changes in static pressure-volume hysteresis and dynamic compliance were reversed by sighing, and histamine effects on the lung were eliminated by 15 minutes after cessation of histamine infusion.

Pharmacodynamic basis for the interaction of cimetidine with the bone marrow stem cells (CFUS).

A histamine H2-receptor agonist, 4-methylhistamine, triggers the pluripotent stem cells of mouse bone marrow from a noncycling state into the DNA synthetic phase of the cell cycle. The histamine H2-receptor blocking agent cimetidine antagonized the action of 4-methylhistamine. The antagonism was reversed by increasing 4-methylhistamine concentrations. When compared at equimolar concentrations with another antagonist, metiamide, cimetidine was more effective than was metiamide at shifting the concentration-response curve of 4-methylhistamine to the right. The data give pharmacodynamic basis for the interaction of histamine-H2-receptor antagonists with bone marrow cells. They also question the hypothesis that the bone marrow toxicity of metiamide was related to the thiouridine group in its structure and that substitution of a cyanoguanidine group for the thiouridine moiety represents a structural modification that would avoid bone marrow effects of histamine-H2-receptor antagonists. Hence, interaction with progenitor cells, e.g., CFUS may be a property of all histamine-H2-receptor antagonists. Pathophysiologic conditions that increase demand for functional hematopoietic cells may represent situations that make bone marrow growth and differentiation susceptible to inhibition by histamine-H2-receptor antagonists.