Submitted on February 26, 2009
Revised on April 9, 2009
Accepted on April 24, 2009
Cardiovascular responses to microinjections of urocortins into the NTS: Role of ionotropic glutamate receptors
Takeshi Nakamura1 and Hreday N. Sapru2*
1 UMDNJ-New Jersey Medical School
2 UMDNJ - New Jersey Medical School
* To whom correspondence should be addressed. E-mail: sapru{at}umdnj.edu.
Urocortin 1 (Ucn1) and urocortin 3 (Ucn3) are a new members of the corticotrophin-releasing factor (CRF) peptide family. Ucn1 is a ligand for both the CRF type 1 receptors (CRF1Rs) and the CRF type 2 receptors (CRF2Rs), whereas, Ucn3 is a high affinity ligand for the CRF2Rs. Recently, we reported that Ucn3 microinjections into the mNTS elicit decreases in mean arterial pressure (MAP) and heart rate (HR) (13). The presence of CRF2Rs on afferent terminals has been reported in the medial nucleus tractus solitarius (mNTS) of the rat. It was hypothesized that activation of CRF2Rs 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 CRF2Rs in the mNTS, by Ucn1 and Ucn3, releases glutamate, which, in turn, elicits decreases in MAP and HR via activation of iGLURs.
