Coupling of histamine H3 receptors to neuronal Na+/H+ exchange: A novel protective mechanism in myocardial ischemia

In myocardial ischemia, adrenergic nerves release excessive amounts of norepinephrine (NE), causing dysfunction and arrhythmias. With anoxia and the concomitant ATP depletion, vesicular storage of NE is impaired, resulting in accumulation of free NE in the axoplasm of sympathetic nerves. Intraneuronal acidosis activates the Na+/H+ exchanger (NHE), leading to increased Na+ entry in the nerve terminals. These conditions favor availability of the NE transporter to the axoplasmic side of the membrane, causing massive carrier-mediated efflux of free NE. Neuronal NHE activation is pivotal in this process; NHE inhibitors attenuate carrier-mediated NE release. We previously reported that activation of histamine H3 receptors (H3R) on cardiac sympathetic nerves also reduces carrier-mediated NE release and alleviates arrhythmias. Thus, H3R activation may be negatively coupled to NHE. We tested this hypothesis in individual human SKNMC neuroblastoma cells stably transfected with H3R cDNA, loaded with the intracellular pH (pHi) indicator BCECF. These cells possess amiloride-sensitive NHE. NHE activity was measured as the rate of Na+-dependent pHi recovery in response to an acute acid pulse (NH4Cl). We found that the selective H3R-agonist imetit markedly diminished NHE activity, and so did the amiloride derivative EIPA. The selective H3R antagonist thioperamide abolished the imetit-induced NHE attenuation. Thus, our results provide a link between H3R and NHE, which may limit the excessive release of NE during protracted myocardial ischemia. Our previous and present findings uncover a novel mechanism of cardioprotection: NHE inhibition in cardiac adrenergic neurons as a means to prevent ischemic arrhythmias associated with carrier-mediated NE release.

Inverse agonism of histamine H2 antagonist accounts for upregulation of spontaneously active histamine H2 receptors.

Histamine H2 receptors transfected in Chinese hamster ovary (CHO) cells are time- and dose-dependently upregulated upon exposure to the H2 antagonists cimetidine and ranitidine. This effect appears to be H2 receptor-mediated as no change in receptor density was observed after H1 or H3 antagonist treatment or after incubation with the structural analogue of cimetidine, VUF 8299, which has no H2 antagonistic effects. By using transfected CHO cells expressing different densities of wild-type H2 receptors or an uncoupled H2Leu124Ala receptor, the histamine H2 receptor was found to display considerable agonist-independent H2 receptor activity. Cimetidine and ranitidine, which both induce H2 receptor upregulation, actually functioned as inverse agonists in those cell lines displaying spontaneous agonist-independent H2 receptor activity. Burimamide, on the other hand, was shown to act as a neutral antagonist and did as expected not induce H2 receptor upregulation after long-term exposure. The displayed inverse agonism of H2 antagonists appears to be a mechanistic basis for the observed H2 antagonist-induced H2 receptor upregulation in transfected CHO cells. These observations shed new light on the pharmacological classification of the H2 antagonists and may offer a plausible explanation for the observed development of tolerance after prolonged clinical use.

Adding Color to Feminism: White Privilege Within the Women's Liberation Movement.

This paper will explore how white privilege has been intertwined with the women's liberation movement in the United States. Feminism and its goals are described briefly and linked to an evaluation of white privilege within the movement. The feminist movement is explored throughout its three waves, including a class and race analysis of each separate period. In addition, this analysis focuses on how Black and Chicana women have been excluded from the mainstream, White, middle-class movement. Through the use of Social Dominance Theory (Sidanius & Pratto, 1999), the prevalence and impact of oppression and hierarchy are explored. The implications of oppression and exclusion in the current political climate are followed by suggestions for aligning the goals and direction of feminism with social justice.

Becoming a State: Zionist and Palestinian Movements for National Liberation

This study examines the road to statehood for the Zionist and Palestinian movements. There are three components which frame this investigation: 1. social movements and the practices in which they engage that are aimed at establishing statehood for a people; 2. distinctive configurations of the international system and the manner in which both the material and ideational foundations of that system pulls units towards conformity and predictable behavior; and finally, 3. the role of agency, that is, the way in which instrumentally rational individuals attempt to push the structure in which they are embedded towards a configuration that is better suited to their interests and objectives The most influential factor guiding these struggles for national liberation are those forces which emanate from the prevailing structure of the international system. Not only was it demonstrated that the established material and ideational preferences of existing states have strong bearing on a movement’s ideological orientation and by consequence its chosen course of struggle, but hegemonic order configurations also define political cleavages and in so doing present movement leaders with both tactical and strategic opportunities by harnessing or exploiting those cleavages. From the agency perspective, the cases showed that the leadership of each movement was highly influential in the determination of a movement’s success or failure.

Liberation, the threat and challenge of power.

Mode of access: Internet.

Experimental post-season liberation of imported cottontail rabbits.

Final report Project W-22-R, Job IV-A.

Narrative of services in the liberation of Chili, Peru, and Brazil, from Spanish and Portuguese domination,

The author was commander of the Chilean navy 1818-1823, and held a like position in Brazil, 1823-1825.

The Liberator : a monthly journal of the Society for the Liberation of Religion from State-Patronage and Control.

Vols. 21-32 also called n.s., v. 1-12.

Memoirs of Maria Antoinetta, Archduchess of Austria, Queen of France and Navarre : including several important periods of the French Revolution, from its origin to the 16th of October, 1793, the day of Her Majesty's martyrdom, with a narrative of the trial and martyrdom of Madame Elizabeth, the poisoning of Louis XVII in the temple, the liberation of Madame Royale, daughter of Louis XVI, and various subsequent events /

Vol. 2 translated by R. May ; v. 3 by Mrs. Ievers.

Travels in the year 1806, from Italy to England, through the Tyrol, Styria, Bohemia, Gallicia, Poland, and Livonia, containing the particulars of the liberation of Mrs. Spencer Smith, from the hands of the French police ...

"Translated from the original mss. in Italian, by W. Fraser."

The finances of European liberation,

Mode of access: Internet.