Vetter T, Lohse MJ. Magnesium and the parathyroid. Institute for Pharmacology and Toxicology, Würzburg, Germany. Curr Opin Nephrol Hypertens. 2002 Jul;11(4):403-10.
I just read the above article on PubMed. I recommend the read, however it's very long, so I'll summarize the mechanism below. By the way, I've read on some forums/threads that Mg2+ is a cofactor for cAMP, which is blatantly wrong. Mg2+ is a cofactor for the production of cAMP, not for the actual molecule itself.
Firstly, Mg2+ and Ca2+ act on the same negative feedback receptor on parathyroid chief cells. The receptor is called CaR. Magnesium is considered a partial agonist because it has 2-3x lesser affinity for CaR than calcium (both Ca and Mg are group2 alkali metals, so it's reasonable that they'd both bind given their 2s electrons).
The activation of CaR induces G-protein activity via both G-alpha-i and G-alpha-q cascades (if you don't know what that means, the chart on the bottom of p.263 in FA runs you through the different G-protein pathways), thereby causing transient cytoplasmic calcium influx, activation of phospholipase-A2, decreased cAMP activity and subsequent inhibited release of PTH. It is the combination of both G-alpha-i and G-alpha-q proteins, as stimulated by CaR, that is required for inhibition of PTH release.
As serum [Mg2+] decreases, CaR activation decreases and PTH secretion increases. This mechanism represents the inverse relationship that we'd expect for both the calcium-PTH relationship as well as the Mg-PTH one.
So far so good.
However, when serum [Mg2+] falls below 0.5mM, the inverse relationship no longer holds and PTH release decreases. This is known as the "paradoxical block of PTH secretion."
As long as [Mg2+] is > 0.5mM, there will always be some degree of Mg2+ binding to CaR, because even though Mg2+ is only a partial agonist of the receptor (decreased Vmax), the receptor's affinity for Mg2+ is still high (low Km).
Now, even though Mg2+ binding to CaR induces inhibitory effects on PTH secretion, its binding at baseline quantities maintains functionality of the PTH-inhibitory cascade, so in the "absence" of Mg2+ (<0.5mM), CaR loses functionality, but in such a fashion that it is constitutively activated, rather than non-signalling.
Therefore, with hypomagnesaemia reaching serum [Mg2+] < 0.5mM, constitutive CaR activity inhibits PTH secretion. This explains why some patients with hypocalcaemia are refractory to Tx with Ca2+ and vitamin D; only restoration of serum Mg2+ will restore serum [Ca2+] when the patient is dual hypocalcaemic and magnesaemic.
I hope that helps. As I said up above, I've read different mechanisms across random forum posts, so I had to go to PubMed to get information that's peer-reviewed.
~Phloston
