Possible role of histamine receptors in the central regulation of immune responses.

The present study was designed to delineate the role of H1- and H2-histamine receptors in the neuro-immune regulation in rats. The effects of H1- and H2-receptor antagonists on humoral and cell-mediated immune (HI and CMI) responses were investigated after intraperitoneal (i.p.) and intra-cerebroventricular (i.c.v.) administration. HI response was assayed by anti-sheep red blood cell (SRBC) antibody titre in presence and absence of 2-mercaptoethanol (2-ME). The CMI responses were evaluated by delayed type hypersensitivity (DTH) reaction (in vivo), i.e., measurement of footpad thickness, and lymphokine activity such as leucocyte migration inhibition (LMI) test (in vitro). On i.p. administration, both H1- (pheniramine and astemizole) and H2-receptor antagonists (ranitidine and cimetidine) were observed to produce significant enhancement of anti-SRBC antibody response. However, only H2- and not H1-receptor blockers were observed to stimulate CMI response significantly. When administered by icv route, only H2-receptor antagonists caused a statistically significant increase in both HI and CMI responses, while the H1-receptor blockers failed to modify the same. Thus, H2-receptors appear to play a major role in the histaminergic mechanisms involved in immunomodulation both at the level of immunocompetent cells active in the peripheral tissues as well as through the central nervous system structures involved in the central regulation of neuro-immune interaction.

Participación de receptores histaminérgicos involucrados en la permeabilidad vascular / Participation of histaminergic receptors involved in vascular permeability

La permeabilidad vascular puede ser modificada por la liberación de histamina endógena como resultado de la presencia de ciertos tiobarbitúricos (tiopental) en el organismo. Esta modificación en la permeabilidad es mediada por la activación del receptor histaminérgico H1, pero es incierta la participación del receptor H2. En este trabajo se evalúa la participación de receptores H1 y H2 durante los cambios de permeabilidad vascular inducidos por histamina, a través de la determinación de concentraciones séricas de albúmina, proteínas totales y globulinas, que indirectamente lo indican. Se formaron 5 grupos de organismos; un control y 4 experimentales denominados grupo A, B, C y D. A los organismos del grupo A se les aplicó histamina IV, 10 µg/Kg de peso, y finalmente al grupo D se le inyectó simultáneamente 0.16 mg/Kg de peso; al grupo C se le inyectó ranitidina IV, 0.13 mg/Kg de peso, y finalmente al grupo D se le inyectó simultáneamente 0.16 mg/Kg de peso y 0.13 mg/Kg de peso de astemizol y ranitidina IV, respectivamente. El grupo A mostró un decremento significativo en las concentraciones de albúmina, proteínas totales y globulinas. En los grupos B, C y D se observó una disminución en la concentración de proteínas totales y globulinas, pero no de albúmina. Estos resultados muestran que los receptores H1 y H2 están involucrados en el aumento de permeabilidad vascular a la albúmina, pero tal vez exista un proceso de permeabilidad diferencial en el cual el paso de globulinas desde la luz vascular hasta el intersticio esté regulado por otro mecanismo

Efectos de la hidrocortisona sobre la secrecion acida en la mucosa gastrica aislada del sapo / Effects of hydrocortisone on acid secretion in the isolated toad gastric mucosa

Los efectos de los esteroides sobre la secreción ácida gástrica han sido estudiados en diferentes efectos de la hidrocortisona sobre la secreción ácida en la mucosa gástrica aislada del sapo (Bufo marinus). La velocidad de secreción de hidrogeniones (QH+) se midió mediante el método "pH stat" de Durbin y Heinz. La hidrocortisona estimúlo significativamente la QH+ en forma dependiente de la dosis. El efecto tendió a alcanzar un máximo con la concentración de 10mM y se mantuvo durant al menos una hora. En la mucosa previamente tratada con cimetidina 1mM, un antagonista específico de los receptores H2 de la histamina, la adición de hidrocortisona 10mM no estimuló la QH+ pero la adición del agonista colinérgico carbacol, sí provocó una estimulación significativa de la velocidad de secreción ácida. En la mucosa gástrica previamente estimulada con la hidrocortisona 5mM, la acción de una dosis submáxima de histamina incrementó la QH+ y este efecto fue de mayor magnitud que el provocado, por la histamina en ausencia del esteroide. Los resultados indican que la hidrocortisona estimula significativamente la secreción ácida en una forma dosis-dependiente en la mucosa gástrica aislada del sapo. Este efecto parece ser dependiente de la activación de los receptores H2

Immunomodulatory effect of cimetidine on the proliferative responses of splenocytes from T. cruzi-infected rats

O efeito imunomodulatorio da Cimetidine (CIM), um antagonista do receptor de histamina-tipo 2, foi avaliado na resposta blastogenica a Con A em celulas de ratos Wistar Furth (WF) infectados pela cepa Y de Trypanosoma cruzi (T.cruzi). Foi observado que apenas na concentracao de "10 POT. -3"M de Cimetidine houve amplificacao da resposta blastogenica de esplenocitos normais a Con A. Entretanto, a capacidade mitogenica de esplenocitos de animais infectados foi restaurada na presenca de molaridades da droga que variaram entre "10 POT. -8" a "10 POT. -3". Os resultados demonstraram que a CIM tem o potencial de modular a resposta mitogenica de celulas de animais infectados pelo T.cruzi, sugerindo um papel imunoregulatorio da histamina e/ou celulas que expressam receptores H2 nesta infeccao.

Aggravating action of clonidine on ethanol-induced gastric lesions: probable mechanism of action.

Large doses of the imidazoline alpha 2 adrenoreceptor agonist clonidine aggravate ethanol-induced gastric lesions. The alpha 2 adrenoceptor antagonist phentolamine, the opioid antagonist naloxone and the H2 antagonist cimetidine do not prevent this action of clonidine suggesting that it is not mediated by alpha 2, opioid or H2 receptors. Further, like clonidine, high doses of phentolamine and cimetidine aggravate gastric lesions per se, suggesting that all three may be acting at a common 'receptor' site, possibly the imidazoline-preferring receptor (IPR).

Blockade by burimamide of the effects of clonidine on cardiac contractility phosphorylase activation and cyclic adenosine monophosphate in isolated guinea pig heart.

Clonidine in a dose-range of 2.5 microgram to 80 microgram caused positive inotropic effect, which was accompanied by increase in the cyclic AMP levels and phosphorylase-activation of the isolated perfused guinea pig heart. Clonidine-induced biochemical and mechanical effects were blocked by burimamide, an H2-receptor antagonist Propranolol (1 x 10(-6)M), phentolamine (1 x 10(-6)M) or reserpine pretreatment, did not affect the clonidine responses on the perfused guinea pig heart. Clonidine reduced the 4-methyl-histamine (H2-agonist) responses of guinea pig heart. Our data suggest that the cardiac effects of clonidine may be due to stimulation of H2-type of receptors.

Evidence for both H and H2-histamine receptors in rabbit atria.

Spontaneously beating isolated atria of rabbits responded to histamine (0.5-16 micrograms/ml) with positive chrono- and inotropism. However, the inotropic response was greater than chronotropic one. The concentration-response curve of histamine for chronotropic effect was markedly shifted to the right in the presence of 0.5 micrograms/ml metiamide (H2-receptor antagonist), which per se augmented the control contractile amplitude in all the experiments. The rightward shift of chronotropic concentration response curve with mepyramine (H1-antagonist) was, however, moderate. On the contrary, the inotropic concentration response curve of histamine was shifted to much greater extent to right with mepyramine (0.62 micrograms/ml) than with metiamide, thus suggesting a greater share of H1 than H2-receptors in the mediation of positive inotropic effect of histamine. The chronotropic effect appears to be mediated predominently by H2-receptors. Unlike metiamide, mepyramine did not alter the spontaneous frequency or amplitude of contraction. The present study, thus lends support for dual histamine receptors in rabbit atria.