title: Systemic cholecystokinin differentially affects baro-activated GABAergic neurons in rat caudal ventrolateral medulla.
abstract: Cholecystokinin (CCK) is released after a meal to promote digestion and satiety. Circulating CCK inhibits splanchnic sympathetic nerve activity (sSNA), which may contribute to postprandial increases in mesenteric blood flow. The CCK-induced sympathoinhibition occurs by activation of vagal afferent nerves and inhibition of a subset of presympathetic rostral ventrolateral medullary (RVLM) neurons. The present study sought to determine whether the caudal ventrolateral medulla (CVLM) may also play a role in the CCK-induced changes in sSNA. Rats were anesthetized with chloralose, artificially ventilated, paralyzed, and prepared for recording arterial pressure (AP), heart rate (HR), sSNA, and activity of individual CVLM neurons. Injection of CCK-8 (8-10 microg/kg, iv) decreased sSNA, AP, and HR. Most baro-activated CVLM neurons were excited by CCK (n = 25, 3.4-fold increase), whereas other baro-activated CVLM neurons were not affected (n = 7) or were inhibited (n = 3). A subset of baro-activated CVLM neurons that were activated (n = 8) or unaffected (n = 2) was confirmed to be GABAergic by the presence of GAD67 mRNA. Bilateral inhibition of the CVLM by microinjections of muscimol reversed the decreases in sSNA and AP to a prominent sympathoactivation and increase in AP (n = 18). These data suggest that systemic injection of CCK leads to the activation of most baro-activated GABAergic CVLM neurons and that the CVLM is essential for the production of CCK-induced inhibition of sSNA. The differential responses of baro-activated GABAergic CVLM neurons to CCK may contribute to the diverse responses of presympathetic RVLM neurons and sympathetic outflows observed with systemic CCK.
authors.affiliation: Department of Physiology, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-3000, USA.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Mobley
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Mandel
authors.forename: Ann M
authors.initials: AM
authors.lastname: Schreihofer
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000502:physiology; D002766:Cholecystokinin / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D008845:Microinjections; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D002395:Catecholamines; D018755:GABA Agonists; D007527:Isoenzymes; D012333:RNA, Messenger; D006830:Hydralazine; D005680:gamma-Aminobutyric Acid; D002766:Cholecystokinin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1