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Studies the effect of hypoxia on norepinephrine (NE)-induced contraction to explain why rabbit pulmonary arteries must be precontracted to observe a hypoxic response. Characteristics of pharmacomechanical coupling induced by NE; Role of extracellular calcium in NE contraction; Effect of caffeine, ryanodine and cyclopiazonic acid on NE-induced phasic contraction.

Presents a study on the hypoxic pulmonary vasoconstriction of rabbits which when given norepinephrine it enhances agonist-induced pulmonary arterial contractions by increasing calcium sequestration. Methodology of the study; Results of the study; Discussion on the study.

Presents a study which examined the effect of hypoxia on spontaneous transient outward currents in intrapulmonary artery smooth muscle cells. Methodology; Results and conclusion.

Background and Purpose: The 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (edelfosine) is an ether-linked phospholipid with promising anti-cancer properties but some side effects that preclude its full clinical therapeutic exploitation. We hypothesized that this lipid could interact with plasma membrane ion channels and modulate their function.Experimental Approach: Using cell migration-proliferation assays, patch clamp, spectrofluorimetry and ¹²⁵I-Apamin binding experiments, we studied the effects of edelfosine on the migration of breast cancer MDA-MB-435s cells, mediated by the small conductance Ca²(+) -activated K(+) channel, SK3/K(Ca)2.3.Key Results: Edelfosine (1 µM) caused plasma membrane depolarization by substantially inhibiting activity of SK3/K(Ca)2.3 channels, which we had previously demonstrated to play an important role in cancer cell migration. Edelfosine did not inhibit ¹²⁵I-Apamin binding to this SK(Ca) channel; rather, it reduced the calcium sensitivity of SK3/K(Ca)2.3 channel and dramatically decreased intracellular Ca²(+) concentration, probably by insertion in the plasma membrane, as suggested by proteinase K experiments. Edelfosine reduced cell migration to the same extent as known SK(Ca) channel blockers. In contrast, K+ channel openers prevented edelfosine-induced anti-migratory effects. SK3 protein knockdown decreased cell migration and totally abolished the effect of edelfosine on MDA-MB-435s cell migration. In contrast, transient expression of SK3/K(Ca)2.3 protein in a SK3/K(Ca)2.3-deficient cell line increased cell migration and made these cells responsive to edelfosine.Conclusions and Implications: Our data clearly establish edelfosine as an inhibitor of cancer cell migration by acting on SK3/K(Ca)2.3 channels and provide insights into the future development of a new class of migration-targeted, anti-cancer agents. [ABSTRACT FROM AUTHOR]

The mechanism of action of halothane is not fully understood in pulmonary circulation and especially in chronic hypertension models. As the 5-hydroxytryptamine (5-HT) pulmonary vasoconstrictor response increases in chronic hypoxic rat, halothane could differentially attenuate this vasoconstriction response on normoxic and chronic hypoxic rats. The effect of halothane on 5-HT-induced contractions on pulmonary arteries isolated from normoxic and chronic hypoxic rats was compared. Rings dissected from proximal pulmonary artery without endothelium were attached to a force transducer to record tone and placed in an organ chamber gassed either by air or air + halothane (1–5%). Contractions induced by (10–4 M) 5-HT were used to test the effect of halothane on rings isolated from normoxic and chronic hypoxic rats. 5-Hydroxytryptamine-mediated contractions were more sensitive to external calcium in normoxic than chronic hypoxic rings. In calcium-free solution, with verapamil or cadmium the amplitude of remaining 5-HT-induced contractions were greater in chronic hypoxic rings. Halothane (1–5%) decreased 5-HT-mediated contractions in normoxic and chronic hypoxic rings. The effect occurred with no change of pD2 for 5-HT and was more pronounced in normoxic rings. The effect of halothane on both rings was abolished in the absence of external calcium or in the presence of verapamil. In the presence of cadmium, 5% halothane had no effect on normoxic rings but still decreased the remaining 5-HT contraction on chronic hypoxic rings. The findings suggested that halothane decreased sarcolemmal calcium entry in pulmonary artery rings by a cadmium-sensitive pathway in normoxic rats and by a cadmium-insensitive pathway in chronic hypoxic rats. [ABSTRACT FROM AUTHOR]

In this short review paper, we report our efforts to design new inhibitors of SK3 ion channel that are involved in cancer cell migration and metastases formation. The originality of the new SK3 inhibitors comes from their amphiphilic nature and contrast form others inhibitors that are peptides or heterocyclic compounds. We found that ether lipids and ether phospho-glyco-lipids are indeed efficient to modulate SK3 ion channel that consequently reduced cancer cell migration (in vitro assays) and abolished the formation of bone metastases in a murine model of breast cancer. [ABSTRACT FROM PUBLISHER]