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.