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J Codina

Publications and source records attributed to J Codina.

143 records · Page 8Linked to original sources
PubMed1983

Stimulation and inhibition of adenylyl cyclases mediated by distinct regulatory proteins.

Adenylyl cyclases are under positive and negative control by guanine nucleotides and hormones. Stimulatory responses are mediated by a guanine nucleotide- and Mg-binding regulatory component (Ns), a protein that has been purified to homogeneity. Inhibitory responses have been hypothesized to be mediated by an analogous regulatory component (Ni) distinct from Ns, but definitive proof for this is lacking and these effects may result from modulation of Ns activity. Recently, Bordetella pertussis toxin has been shown to ADP-ribosylate a peptide that is not part of Ns, and this coincides with attenuation of hormonal inhibition of adenylyl cyclase. We show here that cyc- S49 cells contain a substrate for ADP-ribosylation by pertussis toxin and that the toxin alters GTP dependent inhibition of cyc- adenyl cyclase activity. As cyc- S49 cells do not contain Ns by several criteria, we conclude that Ni is a distinct and separate regulatory component of adenylyl cyclase.

Adenosine Diphosphate Ribose↗
PubMed1983

Pertussis toxin substrate, the putative Ni component of adenylyl cyclases, is an alpha beta heterodimer regulated by guanine nucleotide and magnesium.

The final step in a scheme for the purification of the guanine nucleotide- and Mg2+-binding stimulatory regulatory component (Ns) of adenylyl cyclase [adenylate cyclase; ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] from human erythrocyte membranes involves chromatography over hydroxylapatite (HAP) which yields two fractions. The first fraction (HAP I) contains predominantly two peptides that, upon sodium dodecyl sulfate/polyacrylamide gel electrophoresis, migrate with Mr values of 39,000 and 35,000. The second fraction (HAP II) contains predominantly Ns formed of two peptides of Mr 42,000 and 35,000. The HAP I, Mr 39,000 peptide is shown to be a substrate for the ADP-ribosylating toxin of Bordetella pertussis (pertussis toxin). Upon sucrose density gradient centrifugation, both the Mr 39,000 and the Mr 35,000 peptides of HAP I migrate at about 4 S. Treatment of HAP I with guanine nucleotide and Mg2+ prior to centrifugation results in a coordinated change in the migration of both peptides to 2 S. It is postulated that HAP I contains an alpha beta heterodimeric protein composed of an alpha subunit of Mr 39,000 and a beta subunit of Mr 35,000. Further, this protein dissociates under the influence of guanine nucleotides and Mg2+ into its individual alpha and beta subunits. Because previous studies have shown that treatment of cells and cell membranes with pertussis toxin results in attenuation of the effects of hormones that inhibit adenylyl cyclase activity, and because this effect correlates with the ADP-ribosylation of a Mr approximately equal to 40,000 peptide, we believe that we have purified a guanine nucleotide- and Mg2+-binding inhibitory regulatory component of adenylyl cyclases--i.e., the Ni.

Adenylate Cyclase Toxin↗
PubMed1982

Comparative changes with age of the fasting response in circulating ketone bodies, glucose and insulin and oral glucose tolerance test in the rat.

1. Body weight loss in 48 hr fasted rats decreased with age. 2. Blood glucose and plasma RIA-insulin levels correlated negatively and positively respectively with body weight in fed rats. Fasting produced a greater fall in blood glucose and a smaller decrease in RIA-insulin in young than in old rats. 3. Blood ketone bodies correlated negatively with body weight after 48 hr fasting. 4. In oral glucose tolerance tests, blood glucose rose more in adult and old rats than in prepuberals when both fed and fasted. RIA-insulin levels rose more in prepuberals than in older rats when fed but not when fasted. 5. Changes in body composition and reduced insulin sensitivity with age are discussed.

Aging↗
PubMed1980

Changes in plasma glucose, insulin and glucagon levels, glucose tolerance tests and insulin sensitivity with age in the rat.

Glucose and insulin relationships with aging were studied in fed rats. Levels of basal circulating glucose did not change while those of RIA-insulin increased and RIA-glucagon decreased lineary with animal weight. The oral glucose tolerance test revealed a greater increase in blood glucoe in adult and old rats than in prepuberals, while the rise in plasma insulin was faster and greater in the oldest group. After intravenous glucose load, plasma insulin increase was greater in adult than in prepuberal and old rats, and in the latter grup values remained elevated for a longer period. The hypoglycemic response to i.v. insulin was greatest in the prepuberals with no difference between adult and old rats. In prepuberals, the augmented insulin sensitivity was counteracted by retarded insulinotropic glucose action and an enhanced basal glucagon level, while in the old animals normoglycemia was maintained due to an augmented secretory response of B cells, counteracted by reduced sensitivity to endogenous insulin.

Aging↗
PubMed1979

Effect of fasting on urinary excretion of water and nitrogen in the rat.

Rats housed in metabolic cages undergoing 48 h fasting showed reduced daily intake of drinking water and increased urinary volume. Both the daily amount of urinary creatinine and urea excreted were diminished with fasting, while that of ammonia was augmented. Besides demonstrating metabolic water loss under fasting, results suggest that ammonia derived from glutamine in the kidney, rather than urea formed in the liver, is the main nitrogenous catabolic product of amino acids in fasting.

Animals↗
PubMed1979

Effect of fasting on circulating glucose, ketone bodies and insulin levels in the suckling rat.

Suckling rats from 5 to 30 days of age were subjected to fasting in a 37 degrees C chamber to avoid possible metabolic effects from low environmental temperature. The percentage of body weight loss in 24 h fasting increased along with the age of the rats. Blood glucose levels were the same in 5, 10, 20 and 30 day old animals when fed, whereas fasting produced a fall in all the groups which was minimal in the 20 day old animals. Plasma insulin levels were rather low in 10-day-old fed animals; the maximal decrease in this parameter was reached by 5-day-old rats under fasting. Both beta-hydroxybutyrate and acetoacetate levels were higher in animals of 5 and 10 days of age than in those of 30 days, but fasting did not produce any changes in the former while those parameters augmented in the 20 and 30-day-old animals. The results are discussed in relation to the high fat content in the mother's milk, which affects the metabolic situation of the suckling rats when fed and their response to the fasting situation.

Age Factors↗
PubMed1975

Vectorcardiograms in severe aortic insufficiency. Clockwise rotation of QRS loop in the horizontal plane.

In La Paz Hospital, Madrid, recently, vectorcardiograms (VCGs) were performed on 74 patients with aortic insufficiency. These cases presenting electrocardiographic and radiologic signs of left ventricular hypertrophy, were divided into three groups. In 25 patients (Group 1) the QRS loop in the horizontal plane (HP) showed counterclockwise rotation; 43 patients (Group 2) showed clockwise rotation; and 6 patients (Group 3) showed a pattern of left bundle branch block (LBBB). In Group 2, 31 of the 43 patients (group 2-A) had a Qloop of normal orientation and generally increased voltage, and in the remaining 12 patients (group 2-B) the Q loop was absent. All of the patients in Group 2 had severe aortic insufficiency. Thus, that group's valuation of the left ventricular hypertrophy using maximum QRS vector voltage in the HP, was higher than in Group 1 mean 3.75mV in Group 2 versus mean 2.71mV in Group 1 (p less than 0.01). Postoperative VCGs were performed in 12 patients of group 2-A, showing in all of them a clockwise to counterclockwise rotation change of the QRS loop in the HP. On the other hand, this fact was observed in only two of the eight patients in group 2-B. The clockwise rotation of the QRS loop in the HP is an important datum in our report, particularly in the diagnosis of severe aortic insufficiency. Conversely, a clockwise to counterclockwise rotation change would be a positive sign of good post operative evolution. Finally, two reasons are given to explain this anomalous rotation in the horizontal plane: dilatation and fibrosis.

Adolescent↗
PubMed1975

Vectocardiography in tetralogy of Fallot before and after operation (palliative and corrective surgery).

Vectorcardiograms from 55 patients with diagnosed tetralogy of Fallot were studied and divided into the following three groups: A, 35 nonoperated cases; B, 23 with systemic-pulmonary shunt (nine studied preoperatively and also in A); and C, ten after total correction. In group A, two different types of QRS loop occurred in the horizontal plane (HP); 23 clinically and hemodynamically severe cases had right anterior position with clockwise (C) rotation, and 12 less severe cases had right posterior position with counterclockwise (CC) rotation or figure-8 morphology. In the frontal plane the QRS loop was located inferiorly and to the right, with C rotation (80 percent); two cases had the left anterior hemiblock (LAHB) pattern, and another two severe cases had CC rotation and right superior position. Group B had an evident increase of left ventricular forces in the HP, compared with group A; group-B rotation was preferentially CC or figure-8 morphology. Group C had a pattern of right bundle-branch block in nine cases (classic in one and uncharacteristic in eight); four cases also had LAHB.

Adolescent↗
PubMedDate not supplied

A role for Ni in the hormonal stimulation of adenylate cyclase.

The best understood system for transduction of extracellular messages into intracellular signals is the hormone receptor-coupled adenylate cyclase. In such systems receptors are functionally coupled to the enzyme by two special proteins, termed the stimulatory and inhibitory guanine nucleotide regulatory proteins (Ns and Ni, respectively). These proteins, thought to mediate, respectively, stimulatory and inhibitory influences on the adenylate cyclase, are members of a larger class of heterotrimeric guanine nucleotide regulatory proteins involved in membrane signal transduction. We have studied the interactions of the various components of the adenylate cyclase system by co-reconstituting pure beta-adrenergic receptors, pure Ns and Ni, and functionally resolved preparations of the catalyst in phospholipid vesicles. In the absence of Ni, beta-adrenergic receptor/Ns-mediated catecholamine stimulation of the enzyme is relatively modest (approximately 1.3-fold). Surprisingly, however, when Ni is also present, stimulation increases dramatically (up to 7-8-fold) because of a greater suppression of basal relative to agonist-stimulated enzyme activity. Thus, Ni may actually be required for maximal agonist stimulation as well as for inhibition of the adenylate cyclase.

Adenylyl Cyclases↗