cyclic-gmp and Magnesium-Deficiency

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

The mechanisms underlying the enhanced relaxant responses to sodium nitroprusside (SNP) associated with magnesium (Mg) deficiency were examined using endothelium-denuded thoracic aortas isolated from rats with dietary Mg deficiency. This enhancement of SNP-induced relaxation was abolished or depressed in the presence of methylene blue (a guanylate cyclase inhibitor). The relaxant responses to 8-bromo cyclic GMP (8-Br cGMP; a membrane-permeable cGMP) of thoracic aortas isolated from Mg-deficient rats were enhanced like those to SNP. These enhanced relaxant responses were depressed by tetraethylammonium (a non-specific K+ channel blocker). Charybdotoxin, a large conductance Ca2+-activated K+ (K[Ca]) channel blocker, inhibited 8-Br cGMP-induced relaxations of aortas from Mg-deficient and control rats. Apamin, a small conductance K(Ca) channel blocker, inhibited 8-Br cGMP-induced relaxations of aortas from Mg-deficient, but not control rats. The relaxant responses to cromakalim (an ATP-sensitive K+ channel opener) of the two groups were not significantly different. These ex vivo results show that dietary Mg deficiency in rats leads to increased sensitivity to NO of endothelium-denuded thoracic aortas in vitro and K(Ca) channel activation via cGMP may be involved in this enhancement.

Topics: Animals; Aorta, Thoracic; Cromakalim; Cyclic GMP; Diet; Endothelium, Vascular; In Vitro Techniques; Magnesium Deficiency; Male; Methylene Blue; Muscle Relaxation; Nitric Oxide; Nitroprusside; Potassium Channel Blockers; Potassium Channels; Rats; Rats, Wistar

Hypocalcemia and resistance to exogenous parathyroid hormone have been reported in several clinical states associated with magnesium deficiency. On the basis of such observations, it has been suggested that magnesium depletion per se may result in impaired responsiveness of the adenyl cyclase-adenosine 3',5'-monophosphate (3',5'-AMP) system. To test this hypothesis, 4 wk old male parathyroidectomized rats were maintained on normal or magnesium-deficient diets for 4 wk and their responses to parathyroid hormone compared. Serum magnesium and calcium fell progressively in the magnesium-deficient group. Despite clinical and biochemical evidence of severe magnesium deficiency in these animals, renal production and excretion of 3',5'-AMP in response to parathyroid hormone was normal both in vitro and in vivo. Additionally, administration of either dibutyryl 3',5'-AMP or parathyroid extract to fasting magnesium-depleted rats produced a normal increase in serum calcium. Parathyroid hormone infusion studies demonstrated normal renal and skeletal responsiveness as measured by urinary excretion of calcium, magnesium, phosphate, and hydroxyproline. These data show that the effect of parathyroid hormone on 3',5'-AMP formation and excretion, the responsiveness of skeletal tissue to 3',5'-AMP, and the renal and skeletal system responses to parathyroid hormone are not altered by pure magnesium deficiency in the parathyroidectomized rat.

Topics: Adenosine Monophosphate; Animals; Bone and Bones; Calcium; Cyclic AMP; Cyclic GMP; Femur; Guanine Nucleotides; Hydroxyproline; Kidney; Magnesium; Magnesium Deficiency; Male; Parathyroid Glands; Parathyroid Hormone; Phosphates; Rats