Adiponectin acts in the nucleus of the solitary tract to decrease blood pressure by modulating the excitability of neuropeptide Y neurons.
Adiponectin is an adipocyte derived hormone which acts in the CNS to control autonomic function, energy and cardiovascular homeostasis. Two 7-transmembrane domain receptors, AdipoR1 and AdipoR2, expressed in the hypothalamus and brainstem mediate the actions of adiponectin. The medulla's nucleus of the solitary tract (NTS) is the primary viscerosensory integration site and an important nucleus in the regulation of cardiovascular function. Here we show the localization of both AdipoR1 and AdipoR2 mRNA in the NTS. We have investigated the consequences of receptor activation in response to exogenous application of adiponectin on cardiovascular (blood pressure and heart rate monitoring in vivo), and single neuron (whole cell current-clamp recordings in vitro) function. Microinjection of adiponectin in the medial NTS (mNTS) at the level of the area postrema resulted in a decrease in BP (mean AUC= -2055+/-648.1, n=5, mean maximum effect: -11.7+/-3.6 mm Hg) while similar commissural NTS (cNTS) microinjections were without effect. Patch clamp recordings from NTS neurons in a medullary slice preparation showed rapid (within 200 s of application) reversible (usually within 1000 s following washout) effects of adiponectin on the membrane potential of 62% of mNTS neurons tested (38/61). In 34% (n=21) of mNTS neurons adiponectin induced a depolarization of membrane potential (6.8+/-0.9 mV), while the remainder of mNTS cells influenced by adiponectin (n=17) hyperpolarized in response to this adipokine (-5.4+/-0.7 mV). Post-hoc single cell RT-PCR (ssRT-PCR) analysis of neurons showed that the majority of NPY mRNA positive mNTS neurons were depolarized by adiponectin (7/11), while 4 of these depolarized cells were also GAD67 positive. The results presented in this study suggest adiponectin acts in the NTS to control BP and suggest that such effects may occur as a direct result of the ability of this adipokine to modulate the excitability of discrete groups of neurons in the NTS. These studies identify the mNTS as a new CNS site which adiponectin may act to influence central autonomic processing.
Hoyda
Ted D
TD
Department of Physiology, Faculty of Arts and Science, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Smith
Pauline M
PM
Ferguson
Alastair V
AV
D052242:Adiponectin / Q000008:administration & dosage* / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000008:administration & dosage; D015870:Gene Expression / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*
D052242:Adiponectin; D002317:Cardiovascular Agents; D009478:Neuropeptide Y; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; C504339:adiponectin receptor 1, rat; C506573:adiponectin receptor 2, rat; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1