Altered coupling between aortic adrenergic-receptors and inositol phosphate accumulation in aldosterone hypertension

Conference · Tue Mar 04 23:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6791468

Jones, A W; Bylund, D B; Shukla, S D; Magliola, L; Smith, J M; Ray-Pranger, C; Bailey, B

The authors previous studies of /sup 42/K efflux have shown a 6-10 fold increase in sensitivity to ..cap alpha..-receptor agonists in aortas from rats (AHR) made hypertensive with aldosterone infusion, uninephrectomy plus high salt intake. Analyses of ..cap alpha..-receptor properties, however, showed no significant difference in sub-type, affinity or maximum binding. They initiated this study to determine whether supersensitivity is associated with altered accumulation of inositol phosphates. Aortic strips were equilibrated in /sup 3/H-inositol PSS for 2 hrs, followed by 10 min exposures to inositol (10 mM) PSS then Li (10 mM) PSS. Strips were placed in Li-PSS +/- norepinephrine (NE) for 30 minutes followed by freeze clamping and analyses of inositol phosphates (IP, IP/sub 2/, IP/sub 3/) by standard methods. In controls (C) NE (3 ..mu..M) increased the CPM 2, 14, and 9 fold respectively (p < 0.001). Sufficient CPM were available to analyze the NE concentration effects on IP and IP/sub 2/. NE = 3 ..mu..M yielded similar CPM per cell water in C (n=6) and AHR (n=5). The EC/sub 50/ for AHR was 5-6 fold lower than C for IP (56 +/- 18 versus 300 +/- 130 nM, p < 0.03) and IP/sub 2/ (57 +/- 14 versus 410 +/- 60 nM, p < 0.001). The K/sub a/ for Ne was 480 nM in C and AHR as determined by fractional receptor inactivation with dibenamine. These preliminary findings indicate a close relation in C between ..cap alpha..-receptor occupancy and accumulation of IP and IP/sub 2/, while supersensitivity in AHR is associated with an increased efficacy in coupling between ..cap alpha..-receptors and polyphosphoinositide metabolism.

• Research Organization: Univ. of Missouri Medical School, Columbia
• OSTI ID: 6791468
• Report Number(s): CONF-8604222-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:4; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ALDEHYDES
ALDOSTERONE
ANIMALS
AORTA
ARTERIES
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOSYNTHESIS
BLOOD VESSELS
BODY
CARDIOVASCULAR DISEASES
CARDIOVASCULAR SYSTEM
CORTICOSTEROIDS
DISEASES
DRUGS
ESTERS
HORMONES
HYDROXY COMPOUNDS
HYPERTENSION
ISOTOPE APPLICATIONS
KETONES
KINETICS
LABELLED COMPOUNDS
LIPIDS
MAMMALS
MEMBRANE PROTEINS
MINERALOCORTICOIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PATHOGENESIS
PHOSPHOLIPIDS
PREGNANES
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
STEROID HORMONES
STEROIDS
SYMPATHOMIMETICS
SYMPTOMS
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASCULAR DISEASES
VERTEBRATES