Effects of pH on Vascular Tone in Rabbit Basilar Arteries

Effects of pH on vascular tone and L-type Ca2+ channels were investigated using Mulvany myograph and voltage-clamp technique in rabbit basilar arteries. In rabbitbasilar arteries, high K+ produced tonic contractions by 11+/-0.6 mN (mean+/-S.E., n=19). When extracellular pH (pHo) was changed from control 7.4 to 7.9 ([alkalosis]o), K+-induced contraction was increased to 128+/-2.1% of the control (n=13). However, K+-induced contraction was decreased to 73+/-1.3% of the control at pHo 6.8 ([acidosis]o, n=4). Histamine (10 micrometer) also produced tonic contraction by 11+/-0.6 mN (n=17), which was blocked by post-application of nicardipine (1 micrometer). [alkalosis]o and [acidosis]o increased or decreased histamine-induced contraction to 134+/-5.7% and 27+/-7.6% of the control (n=4, 6). Since high K+- and histamine-induced tonic contractions were affected by nicardipine and pHo, the effect of pHo on voltage-dependent L-type Ca2+ channel (VDCCL) was studied. VDCCL was modulated by pHo: the peak value of Ca2+ channel current (IBa) at a holding of 0 mV decreased in [acidosis]o by 41+/-8.8%, whereas that increased in [alkalosis]o by 35+/-2.1% (n=3). These results suggested that the external pH regulates vascular tone partly via the modulation of VDCC in rabbit basilar arteries.

Regulation of histamine secretion in a mast cell line

La interacción del alergeno con su lg-E específica anclada en la superficie externa de la membrana plasmática del mastocito desencadena la liberación de histamina de dicha célula. Este proceso requiere la presencia de calcio extracelular y de energía bajo la forma de ATP proveniente fundamentalmente de glicólisis donde el lactato es el producto final. La heterogeneidad de los mastocitos ha sido previamente descrita en diversos tejidos de diferentes especies animales. Así, esta línea celular tumoral en ratones LAF1 mostró propiedades similares a las descritas para los mastocitos presentes en la cavidad peritoneal de la rata. Las respuestas metabólicas relacionadas a la secreción de histamina también fueron estudiadas en esta línea de mastocinoma, que exhibieron un comportamiento diferente dependiendo del secretagogo utilizado. En este sentido, una fuerte estimulación de la glicólisis fue observada la presencia de Concanavalina-A en comparación con la estimulación inducida por el A-23187 y el compuesto 48/80. En este modelo experimental se logró establecer relaciones entre la liberación de histamina con el consumo de glucosa, la produción de lactato y la carga adenílica bajo la forma de ATP

Photochemistry and photobiology of actinic erythema: defensive and reparative cutaneous mechanisms

Sunlight is part of our everyday life and most people accept it as beneficial to our health. With the advance of our knowledge in cutaneous photochemistry, photobiology and photomedicine over the past four decades, the terrestrial solar radiation has become a concern of dermatologists and is considered to be a major damaging environmental factor for our skin. Most photobiological effects (e.g., sunburn, suntanning, local and systemic immunosuppression, photoaging or dermatoheliosis, skin cancer and precancer, etc.) are attributed to ultraviolet radiation (UVR) and more particularly to UVB radiation (290-320 nm). UVA radiation (320-400 nm) also plays an important role in the induction of erythema by the photosensitized generation of reactive oxygen species (singlet oxygen ((1)O2))superoxide (O2-) and hydroxyl radicals ((OH) that damage DNA and cellular membranes, and promote carcinogenesis and the changes associated with photoaging. Therefore, research efforts have been directed at a better photochemical and photobiological understanding of the so-called sunburn reaction, actinic or solar erythema. To survive the insults of actinic damage, the skin appears to have different intrinsic defensive mechanisms, among which antioxidants (enzymatic and non-enzymatic systems) play a pivotal role. In this paper, we will review the basic aspects of the action of UVR on the skin: a) photochemical reactions resulting from photon absorption by endogenous chromophores; b) the lipid peroxidation phenomenon, and c) intrinsic defensive cutaneous mechanisms (antioxidant systems). The last section will cover the inflammatory response including mediator release after cutaneous UVR exposure and adhesion molecule expression.

Study of structure-activity relationships for neurotransmitters using molecular electric field mapping: histamine and some of its H2-receptor agonists.

Molecular electric field mapping has been carried out to study structure-activity relationships for neutral and cationic forms of histamine and some of its agonists which are thiazole derivatives. Optimised geometries and Mulliken charges at the atomic sites were obtained using the PM3 method. Electric field values near the N3-H bond in histamine and those near substituents at the C2 position in the agonists have been found to correlate reasonably well with observed activities. Electric fields near the sulphur atom in thiazoles indicate that involvement of this site in hydrogen bonding with the H2-receptor is unlikely.