Intermedin 17–47 does not function as a full intermedin antagonist within the central nervous system or pituitary

A fragment of intermedin (IMD), IMD17–47, has been shown to antagonize the hypotensive effects of intravenous IMD administration; however, the effects of IMD17–47 have not been studied in other systems such as brain and pituitary gland. IMD17–47 was administered intracerebroventricularly (i.c.v.) into male rats alone or prior to administration of IMD; and blood pressure and food and water intakes measured. Multiple doses of IMD17–47 failed to alter basal blood pressure and heart rate, but did partially reverse the stimulatory effects of IMD given i.c.v. on blood pressure and heart rate. A low dose of IMD17–47 by itself significantly increased basal food and water intake. However, a higher dose of the antagonist did not alter food or water intake compared to control treated rats. No dose of IMD17–47 was able to reverse the inhibitory effects of IMD administered i.c.v. on food and water intake. Furthermore, IMD17–47 failed to significantly alter the inhibitory effects of IMD on growth hormone releasing hormone-stimulated growth hormone release from dispersed anterior pituitary cells in culture. A siRNA molecule designed to compromise IMD production was able to reduce brain IMD levels and did, upon i.c.v. administration, cause increased water drinking in male rats. This tool may provide a better method than the use of the IMD17–47 compound to study the role of endogenous IMD within the CNS and pituitary.