Catecholamine hypersensitivity of adenylate cyclase after chemical denervation in rat heart

The muscarinic cholinergic agonist, carbachol, and pertussis toxin were used to examine the functional status of the guanine nucleotide-binding protein that inhibits adenylate cyclase (Gi) in cultured neonatal rat heart myocytes. The isoproterenol stimulation of adenylate cyclase activity in myocyte membranes and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in intact cells (4 days in culture) were insensitive to carbachol (0.1 mM). However, in cells cultured for 11 days, carbachol (0.1 mM) inhibited isoproterenol-stimulated cAMP accumulation by 30%. Angiotensin II (ANG II) was also found to inhibit isoproterenol-stimulated cAMP accumulation in day 11 cells in a dose-dependent manner. Pertussis toxin treatment reversed the inhibitory effects of both ANG II and carbachol, suggesting a role for Gi in the process. Carbachol binding to membranes from day 4 cells was relatively insensitive to guanine nucleotides when compared with binding to membranes from day 11 or adult cells. Furthermore, pertussis toxin-mediated 32P incorporation into a 39- to 41-kDa substrate in day 11 membranes was increased 3.2-fold over that measured in day 4 membranes. These findings support the view that, although Gi is expressed, it is nonfunctional in 4-day-old cultured neonatal rat heart myocytes and acquisition of functional Gi is dependent on culture conditions. Furthermore, the ANG II receptor can couple to Gi in heart.

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Role of beta-adrenoceptor-adenylate cyclase system in the developmental decrease in sensitivity to norepinephrine of neonatal rat heart

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)57784-8 ◽

1988 ◽

Vol 46 ◽

pp. 314

Author(s):

Hikaru Tanaka ◽

Hiroshi Saito ◽

Koki Shigenobu

Keyword(s):

Adenylate Cyclase ◽

Rat Heart ◽

Neonatal Rat ◽

Adenylate Cyclase System ◽

Beta Adrenoceptor ◽

Neonatal Rat Heart

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Computer simulation of ischemic rat heart purine metabolism. I. Model construction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1977.232.4.h386 ◽

1977 ◽

Vol 232 (4) ◽

pp. H386-H393

Author(s):

M. C. Kohn ◽

D. Garfinkel

Keyword(s):

Adenylate Cyclase ◽

Rat Heart ◽

Adenine Nucleotide ◽

Extracellular Fluid ◽

Adenosine Kinase ◽

Inorganic Pyrophosphatase ◽

Rate Laws ◽

Fitting Procedure ◽

Tissue Po2 ◽

Adenine Nucleotide Pool

A model is proposed for the partial depletion of the adenine nucleotide pool in the ischemic perfused rat heart which involves seven enzymes: adenylate cyclase, 3',5'-cyclic AMP phosphodiesterase, 5'-nucleotidase, adenosine kinase, adenosine deaminase, purine nucleoside phosphorylase, and inorganic pyrophosphatase. The computer implementation of this model is in terms of rate laws, several of which were obtained by a systematic least-squares fitting procedure. Depletion of the adenine nucleotide pool is initiated by the release of endogenous noradrenaline into the interstitial fluid, which results from a fall in tissue PO2, and the subsequent activation of adenylate cyclase. In this model the substrate for 5'-nucleotidase is a membrane-bound AMP pool formed by hydrolysis of extracellular fluid and functions as a vasodilator; excess adenosine is incorporated into the tissue by a "permease" with Michaelis-Menten kinetics and converted to AMP, inosine, and hypoxanthine. Alternative mechanisms, such as the deamination of AMP by adenylate deaminase and conversion of AMP to adenine by AMP pyrophosphorylase, were rejected primarily on qualitative biochemical grounds.

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Metabolic and cyclic nucleotide enzyme activities in muscle and nonmuscle cells of rat heart during perinatal development

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y85-014 ◽

1985 ◽

Vol 63 (1) ◽

pp. 78-81 ◽

Cited By ~ 5

Author(s):

Russell T. Dowell

Keyword(s):

Adenylate Cyclase ◽

Muscle Cell ◽

Cyclic Nucleotide ◽

Enzyme Activities ◽

Rat Heart ◽

Citrate Synthase ◽

Heart Function ◽

Cell Metabolism ◽

Adult Rats ◽

Nonmuscle Cells

Enzyme activities related to aerobic metabolism and cyclic nucleotides were evaluated in muscle and nonmuscle cells of rat heart. The perinatal period from weaning to adult was studied. Malate dehydrogenase, citrate synthase, and 3-hydroxyacyl-CoA dehydrogenase activities of nonmuscle cells equal or exceed muscle cell activities in the weanling heart. Aerobic enzymes remain unchanged in nonmuscle cells during growth; however, muscle cell activities are enhanced. Adenylate cyclase and guanylate cyclase activities are higher in heart homogenates of weanling than adult rats. Despite elevated adenylate cyclase activity, cyclic AMP levels are identical in weanling and adult rats. Cyclic GMP levels are twofold higher in weanling than in adult rats. Muscle cell metabolism and cyclic nucleotide levels are associated with growth-related changes in heart function and cellularity, respectively.

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