Prostacyclin-induced hypothermia: Involvement of central histamine H2-receptors

Some of the biological activities of prostacyclin (PGI2) are known to be mediated through cyclic AMP (cAMP). The purpose of this study was to assess the involvement of histamine and serotonin receptors as well as cAMP in the PGI2-induced hypothermia in conscious guinea pig. Intracerebroventricular administration of 50–500 μg/kg PGI2 produced a dose-related hypothermia, whereas its stable metabolite 6-keto prostaglandin F1α had an insignificant effect. Low central doses (10–50 μg/kg) of dibutyryl cAMP (DBC) were hyperthermic, but high doses (100–500 μg/kg) caused hypothermia. Theophylline and low doses of DBC given centrally attenuated the PGI2-induced hypothermia. Mepyramine and methysergide did not antagonize the effects of PGI2 or DBC. However, central administration of metiamide (10–100 μg/kg) attenuated the hypothermic responses to both PGI2 and DBC. These results suggest that histamine H2-receptors are involved in the hypothermia induced by PGI2.