Functional and biochemical responses of cultured heart cells to angiotensin II

Conference · Thu May 01 00:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5096773

Allen, I; Gaa, S; Rogers, T B

The authors have utilized a cultured neonatal rat heart myocyte system to study the molecular mechanisms involved in the stimulation of heart cells by angiotensin II (AII). The intact cultured cells, and membranes from these cells, have specific, high affinity receptors for /sup 125/I-AII and for an AII antagonist, /sup 125/I-Sar/sup 1/,Leu/sup 8/-AII. Binding affinity was in the nanomolar range and was inhibited by guanine nucleotides. Functional studies on intact, beating cells revealed a maximal increase in contractile frequency of 50%, observed at 5 nM AII, with half maximal effects noted at around 1 nM. These responses were reversible and specific as the antagonist, Sar/sup 1/, Ala/sup 8/-AII, inhibited AII-induced chronotropic stimulation. AII (100 nM) had no effect on basal adenylate cyclase activity (20 pmoles cAMP/mg prot/min at 2.5mM Mg/sup 2 +/) in cell membranes. Further, in membranes where cyclase activity was stimulated with isoproterenol (290 pmoles cAMP/mg prot/min at 2.5mM Mg/sup 2 +/), addition of AII had no effect. The cyclase-inhibitory muscarinic agonist, carbachol, also failed to reduce isoproterenol-stimulated activity. In preliminary work with the intact cells, AII again did not alter basal cAMP levels (3-10 pmoles cAMP/mg prot). However, the hormone increased isoproterenol-stimulated cAMP levels by almost 50%. These cells are an excellent system for correlating AII receptor binding with functional and biochemical responses.

• Research Organization: Univ. of Maryland, Baltimore
• OSTI ID: 5096773
• Report Number(s): CONF-8606151-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
AMINES
AMP
ANGIOTENSIN
ANIMALS
AROMATICS
AZAARENES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CELL CULTURES
CELL MEMBRANES
CYCLASES
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
ENZYMES
GLOBULINS
GUANINE
HEART
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LYASES
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NEONATES
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PURINES
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
TRACER TECHNIQUES
VASOCONSTRICTORS
VERTEBRATES