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The present research characterizes a newly discovered ANG II(3-8) (ANG IV) binding site localized in structures associated with memory function (hippocampus, neocortex, cerebellum), as well as other brain stem structures (thalamus, inferior olivary nucleus). This site is not the AT1 or AT2 site that binds angiotensins II (ANG II) and III (ANG III) nor does(More)
Female and male rats were trained to discriminate the kappa opioid agonist (5alpha,7alpha,8beta)-(-)-N-methyl-[7-(1-pyrrolidinyl) -1-oxaspiro(4,5)dec-8-yl]benzeneacetamide (U69,593, 0.13 mg/kg SC) from vehicle using a FR-10 schedule of food reinforcement. Female rats took significantly longer than males to acquire the discrimination (66.9 vs. 44.1 sessions,(More)
The development of navigational strategies to solve spatial problems appears to be dependent on an intact hippocampal formation. The circular water maze task requires the animal to use extramaze spatial cues to locate a pedestal positioned just below the surface of the water. Presently, we investigated the role of a recently discovered brain angiotensin(More)
Divalinal-Ang IV [V psi (CH2-NH2)YV psi (CH2-NH2)HPF] is being employed increasingly as a specific AT4 antagonist. This use, which necessitates a comprehensive physiological and pharmacological evaluation of Divalinal-Ang IV's functional and receptor binding characteristics in order to ensure its efficacy and specificity, was the stimulus for this study(More)
Recent evidence from our laboratory suggests that angiotensin II (AII) is synthesized, stored within cells in the paraventricular nucleus (PVN) of the hypothalamus, and upon appropriate stimulation, released and rapidly converted to angiotensin III (AIII). The present investigation extends these observations by first employing a retrograde tracer to confirm(More)
We report here the discovery of a unique and novel angiotensin binding site and peptide system based upon the C-terminal 3-8 hexapeptide fragment of angiotensin II (NH3(+)-Val-Tyr-Ile-His-Pro-Phe-COO-) (AII(3-8) (AIV)). This fragment binds saturably, reversibly, specifically, and with high affinity to membrane-binding sites in a variety of tissues and from(More)
A new class of angiotensin receptors has recently been identified that exhibits both high specificity and affinity for the hexapeptide (3-8) fragment of angiotensin II, angiotensin IV (AngIV). Here, utilizing radioligand binding, we fully characterize AngIV binding at the AT4 receptor on cultured bovine coronary venular endothelial cells (CVEC), and report(More)
Data are presented describing a new angiotensin binding site in rabbit and guinea pig heart, distinct from AT1 and AT2, that demonstrates high specificity and affinity for the hexapeptide fragment angiotensin II(3-8), which will be referred to here as angiotensin IV (AIV). Equilibrium binding in rabbit heart membranes was achieved in 2 hr at 37 degrees C(More)
A unique angiotensin binding site specific for the hexapeptide, AII(3-8), has been identified in guinea pig hippocampus. This binding site, which is present in the pyramidal cell layer of CA1, CA2, CA3 of the hippocampus and dentate gyrus, binds AII(3-8) with high affinity (KD = 1.29 +/- 0.18 nM) in a saturable manner (Bmax = 449 +/- 62 fmol/mg protein).(More)
The ability of angiotensin IV (AIV) analogs to compete for [125I]AIV binding in heat-treated bovine adrenal membranes was examined. Angiotensin IV displayed a Ki of 2.63 +/- 0.12 nM. Peptides containing mono-substitutions with glycine or the corresponding D-amino acid in positions one, two, or three possessed K(i)s greater than 100 nM. Conversely,(More)