Responsiveness to glucagon in fetal hearts. Species variability and apparent disparities between changes in beating, adenylate cyclase activation, and cyclic AMP concentration.

Martin

Experimental Biology and Medicine

et al. 1974

The polypeptide hormone, glucagon, initiates a number of physiological responses including glycogenolysis, lipolysis, insulin release, and increases in heart rate and myocardial contractility. The actions, like those of many other hormones on their respective target tissues, are thought to be mediated by the activation of the membrane-bound enzyme, adenylate cyclase and the resultant increase in the intracellular concentration of adenosine 3 ', 5 '-monophosphate (cyclic AMP). Following the classic description of the glucagon and epinephrine mediated increases in hepatic cyclic AMP by Sutherland and Rall( 1) and the delineation of cyclic AMP as the mediator of the action of these hormones on glycogenolysis, Sutherland and his coworkers proposed four criteria which should be fulfilled before concluding that the effects of a hormone on its target organ were mediated by cyclic AMP ( 2 ) . These criteria have been fulfilled for the actions of glucagon on the heart. One, glucagon activates adenylate cyclase in broken cell preparations of myocardium (3, 4). Two, glucagon increases cyclic AMP levels in intact, isolated perfused hearts ( 5 ) . Three, the inotropic effects of glucagon are potentiated by the phosphodiesterase inhibitor, theophylline (6). Four, the dibutyryl derivative of cyclic AMP has a positive inotropic effect on heart muscle similar to that of glucagon ( 7 , 8).

Section: Fig 2 Glucagon Activation Of Adenylate Cyclase In Fetal Amentioning

confidence: 99%

mentioning

confidence: 98%

125I-Glucagon Binding and Adenylate Cyclase Activation in the Fetal Rat Heart

Martin

Experimental Biology and Medicine

et al. 1974

“…In the rat, the characteristic of indi vidual organs during days 21 -22 of gestation has been particularly well documented, with examination of the liver from day 16 of ges tation [Devos and Hers, 1974] and at 21 days of gestation [Watts and Gain, 1976]: kidney from 16 days before to 21 days after birth [Burch et al, 1971] and heart from 'less than 16 days of gestation" [Wildenthal et al, 1976] to 21 and 22 days of gestation [Wil denthal et al, 1976;Vinicor et al, 1974;Clark, 1973].…”

Section: Introductionmentioning

confidence: 99%

Glycogen and Enzymes of Glycogen Metabolism in Rat Embryos and Fetal Organs

Gutiérrez-Correa¹,

Hod²,

Passoneau³

et al. 1991

Neonatology

Glycogen content and the enzymes of glycogen metabolism have been measured in the postimplantation rat embryo over a period ranging from 9.5 to 18.5 days of gestation. The earliest periods studied were at days 9.5 and 10.5 of gestation, when the yolk sac becomes vascularized and heart beat is first established. The next intervals were at days 10.5–11.5 when vascular connections via the allantoic placenta are formed. At 14.5 and 18.5 days of development, 4 entire organs were analyzed; heart, liver, kidney and brain. The metabolic apparatus of glycogen metabolism was concentrated in the embryo at 10.5 days, then the heart region, and in the heart itself at later stages.

“…Each fetal mouse heart is cultured individually and is maintained at a gas-medium interface on a stainless steel grid (Wildenthal, 1971). Under control conditions (incubation with at least 30% oxygen and with standard culture medium [minimal essential medium (MEM) GIBCOJ), the hearts beat spontaneously and respond appropriately to pharmacological agents such as isoproterenol (Chen et al, 1979) or glucagon (Wildenthal et al, 1976). The principal characteristic of this preparation is that the myocardium is nourished by diffusion of nutrients from the culture medium, independent of coronary blood flow.…”

mentioning

confidence: 99%

“…By adding pharmacological agents to the culture medium, the effect of these agents on myocardial protection during simulated ischemia can be studied (Wildenthal et al, 1976). In this model, a protective effect has previously been demonstrated with insulin (Wildenthal et al, 1976), hypothermia (Roeske et al, 1977), graded increases in oxygen (Ingwall et al, 1979), and resupply of oxygen and oxidizable substrates after injury (Kloner and Ingwall, 1980).…”

mentioning

confidence: 99%

Inosine: a protective agent in an organ culture model of myocardial ischemia.

Goldhaber¹,

Pohost²,

Kloner³

et al. 1982

Circulation Research

SUMMARY. Fetal mouse hearts in organ culture provide a model of ischemic-like injury in which the myocardial protective effect of pharmacological agents can be studied independent of blood flow. To investigate the potential protective effect of a diffusable purine under ischemic-like conditions, we used 4 mM inosine in fetal mouse heart organ cultures deprived of oxygen and oxidizable substrates for 1-10 hours. We studied hearts (n = 258) immediately after simulated ischemia (early) and after a 20-hour recovery period (late), by utilizing three indices of myocardial viability. Thallium-201 accumulation is an early marker of myocardial viability during injury, whereas the percentage of lactic dehydrogenase release from hearts to culture medium and the percentage of irreversibly injured myocytes assessed by planimetry of midventricular histological sections are late markers, used after recovery from injury. At 10 hours of injury, thallium-201 accumulation was 38% greater in inosine-supplied hearts, 3.50 ± 0.16 vs. 2.54 ± 0.08 (counts/min per mg wet weight)/(counts/min per jul medium) (mean ± SEM) (P < 0.001). After recovery from 10 hours of injury, lactic dehydrogenase release was 29% less in inosine-supplied hearts, 35 ± 3% vs. 49 ± 3% (P < 0.001). After recovery from 8 hours of injury, the percentage of histologically irreversibly injured tissue was 23% less in inosine-supplied hearts, 60 ± 7% vs. 78 ± 3% (P < 0.05). These data indicate that inosine has a protective effect on fetal mouse myocardium during simulated ischemia and suggest that inosine deserves further evaluation. (Circ Res 51:181-188, 1982)