title: Acute repeated intracerebroventricular injections of angiotensin II reduce agonist and antagonist radioligand binding in the paraventricular nucleus of the hypothalamus and median preoptic nucleus in the rat brain.
abstract: Angiotensin II (Ang II) stimulates water and saline intakes when injected into the brain of rats. This arises from activation of the AT1 Ang II receptor subtype. Acute repeated injections, however, decrease the water intake response to Ang II without affecting saline intake. Previous studies provide evidence that Ang II-induced water intake is mediated via the classical G protein coupling pathway, whereas the saline intake caused by Ang II is mediated by an ERK 1/2 MAP kinase signaling pathway. Accordingly, the different behavioral response to repeated injections of Ang II may reflect a selective effect on G protein coupling. To test this hypothesis, we examined the binding of a radiolabeled agonist ((125)I-sarcosine(1) Ang II) and a radiolabeled antagonist ((125)I-sarcosine(1), isoleucine(8) Ang II) in brain homogenates and tissue sections prepared from rats given repeated injections of Ang II or vehicle. Although no treatment-related differences were found in hypothalamic homogenates, a focus on specific brain structures using receptor autoradiography, found that the desensitization treatment reduced binding of both radioligands in the paraventricular nucleus of the hypothalamus (PVN) and median preoptic nucleus (MnPO), but not in the subfornical organ (SFO). Because G protein coupling is reported to have a selective effect on agonist binding without affecting antagonist binding, these findings do not support a G protein uncoupling treatment effect. This suggests that receptor number is more critical to the water intake response than the saline intake response, or that pathways downstream from the G protein mediate desensitization of the water intake response.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; Department of Pharmacology and Physiology, College of Medicine, Georgetown University, Washington, DC 20057, USA. Electronic address: rs1251@nova.edu.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Speth
authors.affiliation: Behavioral Neuroscience Program, Department of Psychology, The State University of New York at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Vento
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.
authors.forename: Eduardo J
authors.initials: EJ
authors.lastname: Carrera
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; Farquhar College of Arts and Sciences, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.
authors.forename: Luz
authors.initials: L
authors.lastname: Gonzalez-Reily
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; Farquhar College of Arts and Sciences, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Linares
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; Farquhar College of Arts and Sciences, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.
authors.forename: Kira
authors.initials: K
authors.lastname: Santos
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; Farquhar College of Arts and Sciences, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.
authors.forename: Jamala D
authors.initials: JD
authors.lastname: Swindle
authors.affiliation: Behavioral Neuroscience Program, Department of Psychology, The State University of New York at Buffalo, Buffalo, NY 14260, USA. Electronic address: danielsd@buffalo.edu.
authors.forename: Derek
authors.initials: D
authors.lastname: Daniels
mesh_terms: D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000378:metabolism; D000804:Angiotensin II / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000378:metabolism; D057912:Angiotensin II Type 2 Receptor Blockers / Q000378:metabolism; D000818:Animals; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D060766:Drinking Water / Q000008:administration & dosage; D007457:Iodine Radioisotopes; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D011301:Preoptic Area / Q000187:drug effects* / Q000503:physiopathology; D011869:Radioligand Assay; D019275:Radiopharmaceuticals; D017207:Rats, Sprague-Dawley; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D013356:Subfornical Organ / Q000187:drug effects / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D002491:Central Nervous System Agents; D060766:Drinking Water; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D044139:Receptor, Angiotensin, Type 2; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; C074793:angiotensin II, Sar(1)-; D015059:1-Sarcosine-8-Isoleucine Angiotensin II
keywords: AT(1) angiotensin receptors; Angiotensin; Brain; Desensitization; Hypertension; Radioligand; Saline intake; Thirst; Water intake
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