cyclic-gmp and Diabetes-Insipidus

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Animals; Calcium; Chemotaxis; Cyclic AMP; Cyclic GMP; Diabetes Insipidus; Glycogen; Humans; Hypersensitivity; Intestinal Mucosa; Lipid Metabolism; Lymphocytes; Methods; Mice; Neoplasms; Nucleotides, Cyclic; Parathyroid Diseases; Phagocytosis; Rats

Topics: Chromatography, Ion Exchange; Cyclic AMP; Cyclic GMP; Diabetes Insipidus; Extracellular Space; Glucagon; Humans; Hyperthyroidism; Hypoparathyroidism; Hypothyroidism; Immune Sera; Inosine Nucleotides; Iodine Radioisotopes; Methods; Nucleotides, Cyclic; Phosphorus Radioisotopes; Protein Kinases; Tritium; 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

Familial hypothalamic diabetes insipidus is an autosomal dominant disorder characterized by deficient vasopressin synthesis. Different point mutations in the vasopressin-neurophysin (VP-NP) precursor gene have been found in affected families. In a Dutch kindred, a single G to T transversion in the NP-encoding exon B of one allele converts the highly conserved glycine 17 to a valine residue. In order to examine whether this point mutation affects the processing and transport of the VP-NP precursor, the normal (HV2) and mutant (MT6) vasopressin cDNAs were stably expressed in the mouse pituitary cell line AtT20. The normal precursor was correctly glycosylated and processed, and NP was detected in the culture medium. Secretion of NP was stimulated by 8-bromo-cAMP, indicating that the normal precursor was targeted to the regulated secretory pathway. In contrast, the mutant precursor was synthesized, but processing and secretion were dramatically reduced. The mutant precursor was core-glycosylated but remained endoglycosidase H-sensitive, suggesting that the protein did not reach the trans-Golgi network. These results were supported by immunocytochemical studies. In HV2 cells, NP derived from the precursor was concentrated in the tips of the cell processes where secretory granules accumulate. In MT6 cells, NP staining was restricted to the endoplasmic reticulum (ER) as determined by colocalization with an ER-resident protein, BiP. These results suggest that the mutation within the conserved part of NP alters the conformation of the precursor and thus triggers its retention in the ER.

Topics: Amino Acid Sequence; Animals; Arginine Vasopressin; Cell Line; Conserved Sequence; Cyclic GMP; Diabetes Insipidus; Fluorescent Antibody Technique; Glycine; Glycosylation; Humans; Mice; Netherlands; Neurophysins; Oxytocin; Pituitary Gland; Pituitary Neoplasms; Point Mutation; Protein Precursors; Recombinant Proteins; Transfection; Valine; Vasopressins

The aim of the present study was to investigate the hormonal control of water-balance in children with diabetes insipidus and to assess safety and efficacy of long-term treatment with oral dDAVP. Plasma atrial natriuretic peptide, plasma renin activity, aldosterone, plasma and urinary cyclic 3'5'-guanosine monophosphate and urinary prostaglandin E2 were measured in eight patients (aged 3-21 y) with central diabetes insipidus. At baseline, 12 h after the last dDAVP dose, patients had hypotonic polyuria but normal plasma sodium concentrations and plasma osmolality relative to a control group. The mean plasma atrial natriuretic peptide concentration in patients (26.2 +/- 2.6 pg/ml) tended to be lower than in controls (36.5 +/- 8.2 pg/ml, mean +/- SEM), although the difference was not significant. Plasma cyclic 3'5' guanosine monophosphate was higher in controls (6.0 +/- 0.6 pmol/ml, mean +/- SEM) than in patients (3.8 +/- 0.3 pmol/ml). Aldosterone, plasma renin activity, urinary cyclic guanosine monophosphate and urinary prostaglandin E2 were similar in the two groups. During 3 h following dDAVP administration, atrial natriuretic peptide levels did not change in patients but decreased significantly in controls to 23.0 +/- 4.0 pg/ml. No adverse reactions, or circulating antibodies against dDAVP, were observed after 3.5 years of oral dDAVP treatment. The average oral dDAVP dosage was similar after 1 and 3.5 years of treatment (906 +/- 406 micrograms/24 h, mean +/- SD). Water-balance is not detectably different from normal in correctly treated diabetes insipidus patients in terms of plasma atrial natriuretic peptide, plasma renin activity and aldosterone levels. Long-term oral dDAVP treatment is safe and efficacious.

Topics: Administration, Oral; Adolescent; Adult; Aldosterone; Atrial Natriuretic Factor; Child; Child, Preschool; Cyclic GMP; Deamino Arginine Vasopressin; Diabetes Insipidus; Dinoprostone; Female; Follow-Up Studies; Humans; Male; Renin; Water-Electrolyte Balance

Topics: Adenosine Triphosphate; Adenylyl Cyclases; Angiotensin II; Animals; Calcitonin; Cell Membrane; Cyclic AMP; Cyclic GMP; Diabetes Insipidus; Guanosine Triphosphate; Hormones; Isoproterenol; Kidney; Kidney Tubules; Magnesium; Male; Norepinephrine; Oxytocin; Parathyroid Hormone; Prostaglandins; Rats; Vasopressins; Water