cyclic-gmp and Hyperparathyroidism

Topics: Asthma; Biomarkers; Cyclic GMP; Diagnostic Techniques, Endocrine; Heart Failure; Humans; Hyperparathyroidism; Liver Diseases; Myocardial Infarction; Neoplasms; Nitric Oxide; Radioimmunoassay; Reference Values; Specimen Handling

Magnesium deficiency (MD) may be either latent: i.e. without disturbances in blood Mg, calcium and intracellular potassium (Ki) or patent, with a rich symptomatology: i.e. with hypomagnesemia, hypocalcemia and decreased Ki. These two aspects are also found with magnesium excess. The discrepancy between these two opposite clinical forms leads one to postulate the existence of a control of Mg homeostasis, efficient in latent forms and deficient in patent forms of Mg disturbances. 4 'endocrine glands', (i.e.) adrenal medulla, parathyroids, thyroid and beta-islets in the pancreas are involved mainly in the homeostatic feed-back systems which regulate both Mg levels and the humoral consequences of the disturbances of Mg metabolism. Moreover, the high stability of intracellular Mg2+ in soft tissues also leads one to postulate the existence of cellular feedback regulatory mechanisms. Parallel variations of insulin and epinephrine secretion represent the first known mechanism which tends to maintain constancy of cellular Mg2+, and, secondarily, of 3':5'-cyclic adenosine monophosphate (cAMP). However, this regulation involves 3 types of side effects; i.e. in MD, the epinephrine-insulin hypersecretion may induce: membrane-depolarizing effects, calcinosis-promoting increase of cellular P and Ca influx, and an increase of the 3':5'-cyclic guanosine monophosphate (cGMP) level--the basic characteristics of cellular MD. These noxious side effects may be antagonized by an increase of taurine (TA) influx into the cell, which is actually stimulated by epinephrine-insulin hypersecretion. TA--and perhaps also gamma-L-glutamyl TA, new parathyroid hormone--may counteract all of these side effects by its membrane-stabilizing, Ca-binding and cGMP level-lowering effects. TA, through these nonspecific functions, and perhaps also through a specific action as an 'Mg-sparing hormone', thus appears to be an important factor in the regulation of Mg homeostasis.

Topics: Adrenal Medulla; Animals; Calcitonin; Calcitriol; Calcium; Cyclic AMP; Cyclic GMP; Homeostasis; Hormones; Humans; Hyperparathyroidism; Insulin; Insulin Secretion; Intestinal Absorption; Kidney; Magnesium; Magnesium Deficiency; Models, Biological; Phosphorus; Potassium

Topics: Calcium; Catecholamines; Circadian Rhythm; Clinical Trials as Topic; Cyclic AMP; Cyclic GMP; Glucagon; Humans; Hyperparathyroidism; Hypoparathyroidism; Kinetics; Methods; Nephrons; Parathyroid Hormone; Reference Values; Thyroid Gland; Vasopressins

Topics: Affective Symptoms; Animals; Asthma; Caffeine; Calcitonin; Calcium; Catecholamines; Circadian Rhythm; Cyclic AMP; Cyclic GMP; Dermatitis, Atopic; Diabetes Insipidus; Glucagon; Growth Hormone; Humans; Hypercalcemia; Hyperparathyroidism; Hypocalcemia; Hypoparathyroidism; Insulin; Organ Specificity; Parathyroid Hormone; Psoriasis; Vasopressins

Topics: Animals; Biological Transport; Creatinine; Cyclic AMP; Cyclic GMP; Escherichia coli; Extracellular Space; Glucagon; Humans; Hyperparathyroidism; Hypoparathyroidism; Kinetics; Parathyroid Hormone; Perfusion; Pseudohypoparathyroidism; Vasopressins

Topics: Calcium; Catecholamines; Circadian Rhythm; Clinical Trials as Topic; Cyclic AMP; Cyclic GMP; Glucagon; Humans; Hyperparathyroidism; Hypoparathyroidism; Kinetics; Methods; Nephrons; Parathyroid Hormone; Reference Values; Thyroid Gland; Vasopressins

Platelet cyclic guanosine monophosphate (cGMP) is produced by soluble guanylate cyclase (sGC), the activity of which is modulated by the activity of nitric oxide (NO) constitutive synthase (cNOS) which, in turn, is activated by a calcium/calmodulin complex. In primary hyperparathyroidism (H-PTH) an increase in platelet free calcium levels is present. In this study we evaluate the platelet cGMP levels, as an expression of NO production, in the presence of 3-isobutyl-1-methylxanthine (IBMX) alone (IBMXcGMP) and after stimulation by ionomycine (IONO; IONOcGMP) and sodium nitroprusside (SNP; SNPcGMP), in eight subjects affected by H-PTH before and after removal of adenoma. Platelet cGMP levels were also measured in seven normal subjects. IBMXcGMP and IONOcGMP were elevated in H-PTH patients compared with normal subjects (1.9 +/- 0.3 vs 0.8 +/- 0.2 fmol/10(6) platelets and 2.7 +/- 0.4 vs 1.4 +/- 0.3; P < 0.02 and P < 0.05 respectively) but SNPcGMP was unaffected (3.9 +/- 0.6 vs 2.5 +/- 0.5). After parathyroidectomy, blood levels of intact parathyroid hormone (i-PTH), total calcium (t-Ca), IBMXcGMP and IONOcGMP all decreased (177.5 +/- 23.9 vs 45.0 +/- 8.8 pg/ml, P < 0.005; 6.5 +/- 0.5 vs 4.6 +/- 0.1 mEq/1, P < 0.005; 1.9 +/- 0.3 vs 0.8 +/- 0.2, P < 0.005; 2.7 +/- 0.4 vs 1.8 +/ 0.3, P < 0.05 respectively), while SNPcGMP was not modified (3.9 +/- 0.6 vs 4.3 +/- 0.9). t-Ca and i-PTH were directly correlated with IBMXcGMP (P < 0.02, rs = 0.613; P < 0.02, rs = 0.576 respectively) and i-PTH was also correlated with t-Ca (P < 0.001), rs = 0.840).. (1) levels of IBMXcGMP and IONOcGMP are high in subjects with H-PTH; (2) after surgery both IBMXcGMP and IONOcGMP decrease to normal values. As IBMXcGMP expresses basal cGMP and IONOcGMP expresses the cGMP after cNOS stimulation, it can be speculated that the increase in NO production could be a mechanism to downregulate the vasoconstriction which may be caused by the high calcium levels in smooth muscle cells. After surgery, together with the normalization of calcium levels, NO production also returned to normal values.

Topics: 1-Methyl-3-isobutylxanthine; Adenoma; Blood Platelets; Calcium; Cyclic GMP; Female; Humans; Hyperparathyroidism; In Vitro Techniques; Ionomycin; Ionophores; Male; Middle Aged; Nitric Oxide; Nitroprusside; Parathyroid Neoplasms; Parathyroidectomy; Phosphodiesterase Inhibitors; Postoperative Period; Stimulation, Chemical; Vasodilator Agents

In order to evaluate the role of the hyperparathyroid state for blood pressure and volume homeostasis, eight patients with primary hyperparathyroidism were studied before and after corrective surgery. Neither noradrenaline induced blood pressure changes nor basal blood pressure were affected by the operation, and the values were the same as in an age- and sex-matched control group. Noradrenaline infusion induced an increase in PTH(1-84) values before (72-86 ng l-1, medians, p < 0.02), in contrast to a decrease after (28 to 19 ng l-1, p < 0.05) operation for primary hyperparathyroidism. Basal plasma atrial natriuretic peptide was lower before than after removal of adenomata (3.2 vs. 4.8 pmol l-1, medians, p < 0.02). Cyclic 3'-5'-guanosine monophosphate was not significantly changed (4.7 vs. 5.5 nmol l-1). Aldosterone was higher before than after surgery (139 vs. 71 pmol l-1, p < 0.02), whereas angiotensin II was unaltered (20 vs. 9 pmol l-1). Arginine vasopressin was higher before than after the operation (0.9 vs. 0.7 pmol l-1, p < 0.05), but urinary excretion of prostaglandin E2 was unchanged. In conclusion primary hyperparathyroidism was not associated with changes in noradrenaline reactivity or basal blood pressure despite derangements of hormones adjusting sodium and water homeostasis. It is suggested that the hormonal changes may be secondary to a relative volume depletion.

Topics: Adult; Aged; Angiotensin II; Atrial Natriuretic Factor; Blood Pressure; Calcium; Cyclic GMP; Dinoprostone; Female; Humans; Hyperparathyroidism; Male; Middle Aged; Norepinephrine; Sodium

An ELISA for cGMP in human plasma and urine using a monoclonal antibody is described. The monoclonal antibody was raised against succinyl cGMP conjugated to human serum albumin. The conjugate was adsorbed to the ELISA plate, giving an immobilized antigen approach which simplifies subsequent assay procedures. As low as 1.56 fmol/well of both plasma and urinary cGMP is measurable. Recoveries of added cGMP in plasma and urine were from 97% to 105%. Intra-assay coefficients of variation were less than 7.0% for plasma and 7.1% for urine samples. Inter-assay coefficients of variation for plasma and urine samples were less than 9.9% and 9.5%, respectively. The values obtained by ELISA correlated well with those by radioimmunoassay (RIA) (plasma: r = 0.96, n = 50; urine: r = 0.98, n = 60).

Topics: Antibodies, Monoclonal; Antibody Specificity; Cyclic GMP; Enzyme-Linked Immunosorbent Assay; Evaluation Studies as Topic; Humans; Hyperparathyroidism; Radioimmunoassay; Reference Standards; Reference Values; Sensitivity and Specificity

To determine whether calcium modulates the action of PTH, we measured the cyclic nucleotide and phosphaturic response to PTH following a 4-h infusion of glucose (day 1) and calcium (day 2). The 12 subjects were selected to provide a range of low, normal, and high endogenous PTH function. PTH stimulated nephrogenous cAMP [185 +/- 31 nmol/100 ml glomerular filtrate (GF)], cyclic guanosine monophosphate (0.44 +/- 0.09 mumol/g creatinine), and phosphate (367 +/- 59 mg P/g creatinine) excretion. Calcium infusion stimulated nephrogenous cAMP excretion in the hypoparathyroid subjects (1.42 +/- 0.35 nmol/100 ml GF) but reduced it in subjects with normal parathyroid function (-2.22 +/- 0.46 nmol/100 ml GF). Calcium infusion stimulated cGMP (0.64 +/- 0.1 mumol/g creatinine) and phosphate (113 +/- 48 P/g creatinine) excretion in all subject groups. Calcium infusion led to a 2-fold increase in the cyclic nucleotide and phosphaturic response to PTH in the normal and hypoparathyroid subjects, but had little effect on the PTH response in hyperparathyroid subjects. The extent to which calcium potentiated the ability of PTH to stimulate nephrogenous cAMP excretion correlated negatively with the basal nephrogenous cAMP excretion (r = -0.685, P less than 0.01). We conclude that calcium potentiates the acute effects of PTH on renal cyclic nucleotide and phosphate excretion. This effect is modified by the basal levels of PTH stimulation of the kidney such that it is reduced in magnitude when basal PTH stimulation is increased.

Topics: Calcium; Cyclic AMP; Cyclic GMP; Drug Synergism; Humans; Hyperparathyroidism; Hypoparathyroidism; Kinetics; Parathyroid Hormone; Phosphates

Topics: Adult; Cyclic AMP; Cyclic GMP; Female; Humans; Hyperparathyroidism; Kidney; Male; Nucleotides, Cyclic; Parathyroid Glands; Parathyroid Hormone; Urinary Calculi

Topics: Calcitonin; Calcium; Cyclic AMP; Cyclic GMP; Humans; Hyperparathyroidism; Hypoparathyroidism; Parathyroid Diseases; Parathyroid Hormone

Topics: Cyclic AMP; Cyclic GMP; Humans; Hyperparathyroidism; Hypoparathyroidism; Parathyroid Hormone

Topics: Adult; Aged; Calcium; Cyclic AMP; Cyclic GMP; Female; Humans; Hypercalcemia; Hyperparathyroidism; Kidney Calculi; Male; Middle Aged; Parathyroid Glands

Topics: Adult; Caffeine; Calcitonin; Calcium; Carcinoma, Bronchogenic; Circadian Rhythm; Cyclic AMP; Cyclic GMP; Diagnosis, Differential; Humans; Hypercalcemia; Hyperparathyroidism; Hypoparathyroidism; Lung Neoplasms; Middle Aged; Osteitis Deformans; Parathyroid Glands; Parathyroid Neoplasms; Physical Exertion; Sarcoidosis