Effects of the calcium-regulating glycoprotein hormone stanniocalcin-1 within the nucleus of the solitary tract on arterial pressure and the baroreceptor reflex

Receptors for the calcium-regulating glycoprotein hormone stanniocalcin-1 (STC-1) have been found within the CNS and whether these receptors exist within the nucleus of the solitary tract (NTS), and their possible role in the regulation of arterial pressure (AP) is unknown. Experiments were done in the rat to: (1) map the distribution of STC-1 receptors throughout NTS using in situ ligand binding that uses a stanniocalcin-alkaline phosphatase (STC-AP) fusion protein; (2) determine whether protein and gene expression for STC-1 exists within NTS using immunohistochemistry, Western blot and real time qPCR; (3) determine the effect of microinjection of STC-1 into NTS on AP and the baroreflex. Cells exhibiting STC-1 binding sites were found mainly within the caudal medial (Sm), gelantinous and commissural subnuclei of NTS. Cells containing STC-1 immunoreactivity were found to overlap those regions of NTS that contained STC-1 receptors. STC-1 protein and gene expression were also found within caudal NTS. In chloralose-urethane–anesthetized rats, microinjections of STC-1 (1.76–176 nM; 20 nl) into the caudal Sm elicited a dose-related decrease in AP. In contrast, injections of a nonbioactive form of STC-1 (STC-1+guanosine 5′-triphosphate [GTP]), the vehicle (0.9% saline), or GTP alone did not elicit cardiovascular responses. Additionally, injection of STC-1 into Sm potentiated the AP responses to electrical stimulation of the ipsilateral aortic depressor nerve. Finally, bilateral injection of STC-1 primary antiserum (1:1000; 100 nl) into Sm elicited a long lasting increase in AP, whereas microinjection of heat inactivated STC-1 antiserum did not alter AP. Taken together these data suggest that endogenous STC-1 signaling in NTS is involved in regulating the excitability of neurons that normally function as components of the baroreceptor reflex controlling AP.

▶Stanniocalcin-1 (STC-1) is a calcium-regulating glycoprotein hormone. ▶STC-1 receptors, protein, and gene expressed in nucleus of the solitary tract (NTS). ▶STC-1 injected into NTS decreases arterial pressure and potentiates the baroreflex. ▶Inhibition of STC-1 receptors in NTS causes hypertension. ▶These data suggest a novel mechanism in NTS controlling of arterial pressure.