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Biomedical subjects

P Hamet

Publications and source records attributed to P Hamet.

At least 253 records · Page 14Linked to original sources
PubMed1982

Cyclic nucleotide phosphodiesterase and aggregation in platelets from diabetic rats.

Platelet aggregation and cyclic nucleotide (cNCL) phosphodiesterase (PDE) have been studied in a new strain of insulin-dependent spontaneously diabetic rat (SDR). The rate of aggregation of washed platelets induced by ADP or ionophore A23187 was decreased in SDR as compared to asymptomatic littermates. The activity of soluble cGMP-PDE was increased in SDR, while no significant difference was observed between SDR and control in soluble and particulate cAMP-PDE activities nor in particulates cGMP-PDE activity. Furthermore, a kinetic study of soluble cGMP-PDE in platelets demonstrated that the apparent Km was lower while the Vmax was higher in SDR. Increases were also observed in the activities of particulate cAMP-PDE and cGMP-PDE at low and high substrate concentrations in liver and heart of SDR. These anomalies of platelet aggregation and cNCL-PDE in SDR were partially correctable by insulin. For comparison, a similar study was performed in streptozotocin-induced diabetic rats (STZ). In contrast to SDR, the rate of platelet aggregation induced by ADP was increased in STZ, and the activity of soluble cGMP-PDE in platelets was decreased in STZ. A similar decrease in the activities of cAMP-PDE in liver was also observed in STZ. This study confirms observations concerning the decrease of cGMP-PDE in tissues of STZ diabetic rats. However, since opposite anomalies in PDE activity as well as a platelet function were observed in another model of diabetes (SDR), the significance of these anomalies in the pathophysiology of diabetes requires further investigation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1982

The hemodynamic relevance of free and conjugated dopamine in pheochromocytoma.

Two patients with adrenomedullary hypersecretion (confirmed pheochromocytoma and adrenomedullary hyperplasia) presented 15 spontaneous crises associated with hypertension or hypotension with or without tachycardia. Correlation coefficients calculated between extreme values of pulse rates and of systolic and diastolic blood pressures on the one hand and plasma free and conjugated norepinephrine, epinephrine, and dopamine (DA) sampled at the height of the crises on the other, showed no relationships between free or conjugated norepinephrine or epinephrine and blood pressure or pulse rate. However, plasma conjugated DA was negatively correlated with systolic blood pressures (P less than 0.02) and diastolic blood pressures (P less than 0.03) and free plasma DA was negatively correlated with pulse rates (P less than 0.001). These data suggest that the extremely high circulating level of conjugated DA in pheochromocytoma may, in the presence of high circulating conjugated norepinephrine and possibly high alpha-adrenergic receptor occupancy, decrease blood pressure by its predominant action on dopaminergic receptors while elevated free DA may decrease the tendency to tachycardia, possibly by lowering the venous return.

Adrenal Gland Neoplasms↗
PubMed1982

Stimulation of rat platelet adenylate cyclase by an endogenous calcium-dependent protease-like activity.

The stimulation of adenylate cyclase by various exogenous proteases has been described in several tissues. In this study, we describe a 2 to 7-fold increase of adenylate cyclase activity in a particulate preparation from rat platelets following prior exposure of the homogenate to calcium. Calmodulin alone was unable to increase the adenylate cyclase activity and trifluoperazine only partially inhibited the calcium-dependent activation. On the other hand, calcium had a slight stimulatory effect on the particulate preparation but this activation was greatly enhanced by the addition of supernatant. Only the combined addition of calcium, supernatant and calmodulin to washed particulate preparations reconstituted the activation seen in homogenates. The activation was significantly inhibited by leupeptin and thiol reagents. It is concluded that platelets contain a calcium-dependent protease-like activity that is able to increase adenylate cyclase activity in membrane fractions. This phenomenon may be involved in the regulation of adenylate cyclase activity in platelets.

Adenylyl Cyclases↗
PubMed1982

Primary hyperaldosteronism: a pituitary--adrenal dysfunction related to a new pituitary glycopeptide?

A novel glycopeptide has been isolated from human and porcine pituitary glands. This substance is the amino-terminal fragment of pro-opiomelanocortin (POMC). The complete amino acid sequence has been determined. When tested for its steroid stimulating activity on an aldosterone secreting human adrenocortical adenoma, it was found to be more potent than angiotensin and ACTH. These results raise the interesting possibility that primary hyperaldosteronism could be related to a pituitary adrenal dysfunction.

Adenoma↗
PubMed1981

Basis of false-positive glucagon tests for pheochromocytoma.

In more than half of 67 patients suspected of having pheochromocytoma, glucagon stimulation increased plasma free norepinephrine (NE) and epinephrine (E) 50% or more, with rising blood pressure or pulse rate; only three patients, however, harbored a pheochromocytoma. A low degree of catecholamine conjugation accounts for most of the false-positive results. In patients with low conjugated NE +E there was a greater rise in free NE +E and free E as well as in pulse rate after glucagon stimulation than in those with normal levels of conjugated NE+E. Glucagon-sensitive adenylate cyclase was found in pheochromocytomas but not in a functional adrenocortical adenomas. After sham administration of glucagon, there were rises in blood pressure but not in free NE or E in four patients. The glucagon-induced catecholamine test can be false-positive in hyperadrenergic essential hypertensive patients with abnormally low conjugated NE +E. Saline alone in a sham glucagon test in susceptible patients raises systolic blood pressure and pulse rate, and therefore, if plasma free NE and E are measured and found not to rise this type of false-positive result can be eliminated.

Adenylyl Cyclases↗
PubMed1981

Effect of N-terminal portion of pro-opiomelanocortin on aldosterone release by human adrenal adenoma in vitro.

An adrenal cortex adenoma, surgically removed from a female patient with primary aldosteronism, was used to examine the effect of ACTH, angiotensin II, gamma 3-MSH, and the N-terminal fragment of pro-opiomelanocortin purified from porcine anterior pituitaries on aldosterone release in vitro. Primary cultures of tumor cells were incubated as a monolayer in a 96-well microtitration plate and the aldosterone release was measured in the incubation medium after 2 h of incubation in the presence of absence of different concentrations of the peptides. On a molar basis, the N-terminal portion of pro-opiomelanocortin seems to have the highest activity of all of the peptides assayed.

Adenoma↗
PubMed1980

Characteristics of a new binding protein distinct from the kinase for guanosine 3':5'-monophosphate in rat platelets.

A new type of cyclic GMP binding protein was recently identified in our laboratory (Hamet, P. and Coquil, J.-F. (1978) J. Cyclic Nucleotide Res. 4, 281--290). The binding, recovered in the supernatant fractions, is highly specific for cyclic GMP and is clearly distinct from the binding to cyclic GMP-dependent protein kinase. Chromatography on DEAE-Sepharose separated the cyclic GMP binding protein from cyclic AMP binding, cyclic AMP-dependent kinase activities, and from guanylate cyclase. The optimal binding occurs at high pH and in the presence of thiol reagents. Several phosphodiesterase inhibitors increase the affinity of binding (Kd was 353 +/- 60 nM in the absence and 13.4 +/- 1.5 nM in the presence of 1-methyl-3-isobutyl-xanthine). The molecular weight of the binding protein was determined to be about 176,000 and the sedimentation coefficient was 6.4 S. While the binding and phosphodiesterase activities co-migrated on DEAE-Sepharose, gel filtration and sucrose gradients, certain treatments (such as increasing the concentrations of salt and heating) were able to influence one activity while having no effect on the other. Hence, the binding activity may be involved in the regulation of the activity of cyclic GMP phosphodiesterase. Since the binding protein appears to be the only 'receptor' for cyclic GMP detectable in platelets, this protein and/or its relation to cyclic GMP phosphodiesterase may play a role in the mechanism of action of cyclic GMP in platelets.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1980

Treatment of refractory hypertension with minoxidil.

Twenty patients with hypertension refractory to conventional therapy were treated with minoxidil in combination with a diuretic and a beta-blocker. The mean supine initial blood pressure was 207/128 mm Hg, and the end-treatment pressure was 155/89 mm Hg. Five of the 7 patients with essential hypertension were adequately controlled, as were 8 of the 9 patients with renal failure and all 4 patients with renovascular hypertension. Thus, the overall controll rate was 85%. The duration of treatment ranged from 1 to 30 months, and the minoxidil dosage ranged from 5 to 60 mg/dry electrocardiographic changes characterized by T-wave inversion after starting minoxidil. These changes were reversible in 4 patients. Minoxidil was found to be an effective antihypertensive drug in these patients with refractory hypertension.

Adult↗
PubMed1980

Cyclic nucleotides and platelet aggregation in hypertensive rats with ectopic pituitary tumor.

The transplantable pituitary tumor MtT-F4 secretes several pituitary hormones in Fisher rats, resulting in severe cardiovascular disease with a mineralocorticoid type of hypertension and hyperlipidemia. The mineralocorticoid-dependent hypertension possesses particular characteristics in humans and animals. It was of interest to study cyclic nucleotides and platelet aggregation in the Fisher rat with an MtT-F4 tumor in order to evaluate the type of abnormalities in this form of hypertension. The effect of administration of an anti-hyperlipidemic agent (clofibrate) was also evaluated. The animals bearing the tumor showed anomalies of platelet aggregation induced by the divalent cation ionophore A 23187, in that there was an apparent enhanced change in shape and a decreased rate of aggregation. Although the basal concentrations of cyclic nucleotides were normal, as were the increases in cyclic GMP induced by epinephrine, cyclic AMP concentrations increased less (about 2.7-fold) in response to PGE1 than in control Fisher rats (about 6-fold). A decreased stimulation of adenylate cyclase activity by PGE1 was observed in platelets of tumor-bearing rats. The administration of clofibrate to sham-operated animals somewhat lowered the increase of cyclic AMP in response to PGE1. In tumor-bearing animals, clofibrate considerably reduced plasma lipids, blood pressure and the degree of abnormalities in platelet aggregation and cyclic AMP in platelets. Thus, the abnormalities of platelet aggregation and regulation of cyclic nucleotides in the mineralocorticoid-type of hypertension induced by MtT-F4 were opposite to those found previously in spontaneous hypertension in rats. Hyperlipidemic and hypertensive rats with MtT-F4 tumor may provide a useful model for the study of the relatioship between hyperlipidemia and hypertension.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1980

Preparation of cyclic nucleotide antisera with thyroglobulin-cyclic nucleotide conjugates.

Antisera to cyclic AMP and cyclic GMP were obtained by immunizing rabbits with antigens prepared by conjugating the 2'0-succinyl derivative of the cyclic nucleotides to thyroglobulin. The cyclic nucleotide-thyroglobulin conjugates were injected intradermally into multiple sites on the backs of the animals. This immunization procedure resulted in the production of antiserum in four of five animals capable of binding at a final serum dilution of greater than 1:10,000, 20% of the corresponding iodinated cyclic nucleotide derivative added. The antisera were also highly specific. The antiserum for cyclic AMP had a 2500-fold or greater relative affinity for cyclic AMP than other nucleotides or nucleosides, while that for cyclic GMP had a 5000-fold or greater affinity for 2'0 acetylated nucleotides or nucleosides except for acetylated cyclic IMP. The obstacles to measuring cyclic nucleotides, particularly cyclic GMP, in tissues were also overcome by refining and simplifying the methods for iodination, purification and assay. Furthermore, a "disequilibrium" incubation was developed as an alternative to the acetylation method to increase the sensitivity of the radioimmunoassay. Thus, the levels of both cyclic GMP and cyclic AMP can be determined rapidly and easily in the same tissue sample.

Animals↗
PubMed1980

Conjugation of catecholamines, a variable to be accounted for in human hypertension.

A subgroup of essential hypertensive (EH) patients with high sympathetic tone had low plasma conjugated norepinephrine (NE) and epinephrine (E), but elevated free NE and E and a hyperresponsiveness to various stimuli to the autonomic nervous system. Pheochromocytoma patients could also be divided according to conjugated NE + E levels, this time into normal and elevated conjugated groups. The latter seem to be somewhat protected by the conjugation, showing less free NE and E 'flooding' during hypertensive crises and lower VMA excretion. The degree of catecholamine conjugation can thus modify the sympathetic tone in hypertension.

Adrenal Gland Neoplasms↗