sauvagine and 2-3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline

Urocortin 1 (Ucn1) and urocortin 3 (Ucn3) are new members of the corticotrophin-releasing factor (CRF) peptide family. Ucn1 is a ligand for both the CRF type 1 receptors (CRF(1)Rs) and the CRF type 2 receptors (CRF(2)Rs), whereas Ucn3 is a high-affinity ligand for the CRF(2)Rs. Recently, we reported that Ucn3 microinjections into the medial nucleus tractus solitarius (mNTS) elicit decreases in mean arterial pressure (MAP) and heart rate (HR) (Nakamura T, Kawabe K, Sapru HN. Am J Physiol Heart Circ Physiol 296: H325-H332, 2009). The presence of CRF(2)Rs on afferent terminals has been reported in the mNTS of the rat. It was hypothesized that activation of CRF(2)Rs on afferent terminals in the mNTS may release glutamate, which, in turn, may elicit decreases in MAP and HR via activation of ionotropic glutamate receptors (iGLURs). This hypothesis was tested in urethane-anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (100 nl) of Ucn1 (0.12 mM) into the mNTS elicited decreases in MAP and HR. The responses were partially blocked by microinjections of iGLUR antagonists into the mNTS. On the other hand, the decreases in MAP and HR elicited by microinjections of Ucn3 (0.06 mM) into the mNTS were completely blocked by microinjections of iGLUR antagonists into the mNTS. These results indicate that activation of CRF(2)Rs in the mNTS, by Ucn1 and Ucn3, releases glutamate, which, in turn, elicits decreases in MAP and HR via activation of iGLURs.

Topics: Amphibian Proteins; Aniline Compounds; Animals; Corticotropin-Releasing Hormone; Excitatory Amino Acid Antagonists; Glutamic Acid; Heart Rate; Male; Microinjections; Peptide Hormones; Pyrimidines; Quinoxalines; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone; Receptors, Glutamate; Solitary Nucleus; Sympathetic Nervous System; Urocortins