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

• Published in: Neuroscience Vol. 207; pp. 88 - 102
• Main Authors: Ciriello, J, Oiamo, T.H, Moreau, J.M, Turner, J.K, Wagner, G.F
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 05.04.2012; Elsevier
• Subjects: Animals; baroreflex; Baroreflex - drug effects; Baroreflex - physiology; Biological and medical sciences; Blood Pressure - drug effects; Blood Pressure - physiology; cardiovascular responses; Fundamental and applied biological sciences. Psychology; Glycoproteins - genetics; Glycoproteins - pharmacology; Glycoproteins - physiology; heart rate; Male; Neurology; Rats; Rats, Wistar; Receptors, Cell Surface - agonists; Receptors, Cell Surface - physiology; Recombinant Fusion Proteins - pharmacology; Solitary Nucleus - drug effects; Solitary Nucleus - physiology; stanniocalcin-1 immunohistochemistry; stanniocalcin-1 protein and gene expression; stanniocalcin-1 receptors; Vertebrates: nervous system and sense organs; com; lateral subnucleus of the nucleus of the solitary tract complex; St; GTP; intermediate subnucleus of the nucleus of the solitary tract complex; STC; baroreflex; real-time quantitative reverse transcriptase polymerase chain reaction; HR; ADN; phosphate-buffered saline; hSTC-1; ventrolateral subnucleus of the nucleus of the solitary tract complex; commissural subnucleus of the nucleus of the solitarytract complex; Cu; cuneate nucleus; interstitial subnucleus of the nucleus of the solitary tract complex; hypoglossal nucleus; messenger ribonucleic acid; qPCR; Sdl; Hanks' balanced salt solution; STC-1; 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; PBS; 4V; SDS; nucleus gelatinous of the nucleus of the solitary tract complex; nucleus of the solitary tract; central subnucleus of the nucleus of the solitary tract complex; fourth ventricle; stanniocalcin-1 receptors; ap; SInt; STC-AP; MAP; nitro-blue tetrazolium chloride and 5-bromo 4-chloro 3′indolyphosphate p-toluidine salt; stanniocalcin-1; Tween Tris-buffered saline; guanosine 5′-triphosphate; medial subnucleus of the nucleus of the solitary tract complex; Svl; mRNA; NTS; 12M; stanniocalcin-1 immunohistochemistry; Sni; area postrema; stanniocalcin-1 protein and gene expression; HBHA; NBT-BCIP; sodium dodecyl sulfate; dorsal motor nucleus of the vagus; cc; stanniocalcin; heart rate; dorsolateral subnucleus of the nucleus of the solitary tract complex; central canal; mean arterial pressure; GR; recombinant human stanniocalcin-1; DMV; cp; choroid plexus; Sc; solitary tract; arterial pressure; Sg; nucleus gracilis; stanniocalcin-alkaline phosphatase fusion protein; HEPES; TTBS; Sl; Sm; aortic depressor nerve; cardiovascular responses; Hormone; Immunohistochemistry; Reflex; Calcium; Central nervous system; Glycoprotein; Gene expression; Encephalon; Solitary nucleus; Heart rate; Baroreflex; Arterial pressure; Hemodynamics; Baroreceptor; Biological receptor
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2012.01.044

Abstract 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.