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. (C) 2007 Elsevier Inc. All rights reserved.