Download J Pharmacol Sci - Substance P: Clinical Insights

J Pharmacol Sci. 2009 Jul;110(3):397-400. Epub 2009 Jul 1.
Modulation of the substance P release from cultured rat primary afferent
neurons by zinc ions.
Tang HB, Miyano K, Nakata Y.
College of Pharmacy, South-Central University for Nationalities, Wuhan, China.
The present study was conducted to determine whether zinc ions are involved in the modulation of
substance P release from cultured rat dorsal root ganglion (DRG) neurons. We show here that that lower
concentrations (10(-8) - 10(-7) M) of zinc ions may evoke an extracellular Ca(2+) influx through L-, N-, and
T-type voltage-dependent Ca(2+) channels, thereby increasing the substance P release from cultured DRG
neurons, but higher concentrations (10(-6) - 10(-4) M) of zinc ions attenuate or even completely mask these
responses. Zinc ions therefore seem to be an important modulator of substance P release from primary
afferent neurons.
PMID: 19571463 [PubMed - indexed for MEDLINE]
J Am Coll Nutr. 2009 Apr;28(2):131-41.
Skeletal and hormonal effects of magnesium deficiency.
Rude RK, Singer FR, Gruber HE.
USC Keck School of Medicine, Los Angeles, CA, USA. [email protected]
Magnesium (Mg) is the second most abundant intracellular cation where it plays an important role in enzyme
function and trans-membrane ion transport. Mg deficiency has been associated with a number of clinical
disorders including osteoporosis. Osteoporosis is common problem accounting for 2 million fractures per
year in the United States at a cost of over $17 billion dollars. The average dietary Mg intake in women is
68% of the RDA, indicating that a large proportion of our population has substantial dietary Mg deficits. The
objective of this paper is to review the evidence for Mg deficiency-induced osteoporosis and potential
reasons why this occurs, including a cumulative review of work in our laboratories and well as a review of
other published studies linking Mg deficiency to osteoporosis. Epidemiological studies have linked dietary
Mg deficiency to osteoporosis. As diets deficient in Mg are also deficient in other nutrients that may affect
bone, studies have been carried out with select dietary Mg depletion in animal models. Severe Mg
deficiency in the rat (Mg at <0.0002% of total diet; normal = 0.05%) causes impaired bone growth,
osteopenia and skeletal fragility. This degree of Mg deficiency probably does not commonly exist in the
human population. We have therefore induced dietary Mg deprivation in the rat at 10%, 25% and 50% of
recommended nutrient requirement. We observed bone loss, decrease in osteoblasts, and an increase in
osteoclasts by histomorphometry. Such reduced Mg intake levels are present in our population. We also
investigated potential mechanisms for bone loss in Mg deficiency. Studies in humans and and our rat model
demonstrated low serum parathyroid hormone (PTH) and 1,25(OH)(2)-vitamin D levels, which may
contribute to reduced bone formation. It is known that cytokines can increase osteoclastic bone resorption.
Mg deficiency in the rat and/or mouse results in increased skeletal substance P, which in turn stimulates
production of cytokines. With the use of immunohistocytochemistry, we found that Mg deficiency resulted in
an increase in substance P, TNFalpha and IL1beta. Additional studies assessing the relative presence of
receptor activator of nuclear factor kB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG), found
a decrease in OPG and an increase in RANKL favoring an increase in bone resorption. These data support
the notion at dietary Mg intake at levels not uncommon in humans may perturb bone and mineral
metabolism and be a risk factor for osteoporosis.
PMID: 19828898 [PubMed - indexed for MEDLINE]