Increased expression of alpha 1-adrenergic receptors in the hypothalamus of spontaneously hypertensive rats.
The specificity and molecular weights of alpha 1-adrenergic receptors in various tissues of spontaneously hypertensive (SH) rat were compared with normotensive controls (Wistar-Kyoto; WKY) with the use of [125I]HEAT and [125I]azidoprazosin, specific alpha 1-adrenergic receptor antagonists. Binding of [125I]HEAT to membranes prepared from SH rat brain hypothalamus was significantly higher, due to a 75% increase in the Bmax, than the WKY control. In contrast, the Bmax and Kd of [125I]HEAT binding to brainstem and liver membranes from SH rats were not significantly different from those of WKY controls. Competition-inhibition data suggested similar pharmacological specificity with potencies in the order of prazosin greater than yohimbine greater than propranolol for both WKY and SH rat membranes prepared from liver, hypothalamus, brainstem and neuronal cultures. Photoaffinity labeling of alpha 1-adrenergic receptors from hypothalamus, brainstem and neuronal cultures using [125I]azidoprazosin followed by SDS-PAGE and autoradiography showed the presence of one major band with a molecular weight (MW) of 105,000 Da for both WKY and SH rats. In contrast, labeling of liver alpha 1-adrenergic receptors revealed one major band with a MW of 60,000 Da. Quantitation of the 105,000-Da band from SH rat hypothalamic membranes demonstrated a 52% higher intensity compared with WKY controls. Neuronal cultures prepared from 1-day-old SH rats showed a similarly greater intensity of the 105,000-Da band compared with WKY controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Bottiglieri
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DF
Department of Physiology, University of Florida, College of Medicine, Gainesville 32610.
Morse
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CA
Baker
S P
SP
Crews
F T
FT
Sumners
C
C
Raizada
M K
MK
D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012016:Reference Values; D013045:Species Specificity
D011942:Receptors, Adrenergic, alpha