Calcitonin interaction

Most GPCRs interact with and activate more than one G-protein subfamily, e.g., with Gs plus Gq/n (histamine H2, parathyroid hormone and calcitonin recqrtors), Gs plus G (luteinising hormone receptor, 32-adrenoceptor) or Gq/11 plus G12/13 (thromboxane A2, angiotensin ATb endothelin ETA receptors). Some receptors show even broader G-protein coupling, e.g., to Gi, Gq/n plus Gi n ( protease-activated receptors, lysophosphatidate and sphingosine-1-phosphate receptors) or even to all four G-protein subfamilies (thyrotropin receptor). This multiple coupling results in multiple signaling via different pathways and in a concerted reaction of the cell to the stimulus. 

More than 99% of total body calcium is found in bone the remaining less than 1% is in the ECF and ICE Calcium plays a critical role in the transmission of nerve impulses, skeletal muscle contraction, myocardial contractions, maintenance of normal cellular permeability, and the formation of bones and teeth. There is a reciprocal relationship between the serum calcium concentration (normally 8.6 to 10.2 mg/dL [2.15 to 2.55 mmol/L]) and the serum phosphate concentration that is regulated by a complex interaction between parathyroid hormone, vitamin D, and calcitonin. About one-half of the serum calcium is bound to plasma proteins the other half is free ionized calcium. Given that the serum calcium has significant protein binding, the serum calcium concentration must be corrected in patients who have low albumin concentrations (the major serum protein). The most commonly used formula adds 0.8 mg/dL (0.2 mmol/L) of calcium for each gram of albumin deficiency as follows ... 

Wagner K, Van Mau N, Boichot S, Kajava AV, Krauss U, Le Grimellec C, Beck-Sickinger A, Heitz F (2004) Interactions of the human calcitonin fragment 9-32 with phospholipids a monolayer study. Biophys J 87 386-895. 

The Ca -selective hormones calcitriol, parathyroid hormone, and calcitonin influence this interaction in the bone cells. Parathyroid hormone promotes Ca "" release by promoting the release of cytokines by osteoblasts. In turn, the cytokines stimulate the development of mature osteoclasts from precursor cells (bottom). Calcitonin inhibits this process. At the same time, it promotes the development of osteoblasts (top). Osteoporosis, which mainly occurs in women following the menopause, is based (at least in part) on a reduc-... 

Wiesenfeld-Hallin, Z., Hokfelt, T., Lundberg, J.M., Forssmann, W.G., Reinecke, M., Tschopp, F.A., Fischer, J.A. immunoreactive calcitonin gene-related peptide and substance P coexist in sensory neurons to the spinal cord and interact in spinal behavioural responses to the rat, Neurosci. Lett. 1984, 52, 199-203. 

PTH works with two other primary hormones— calcitonin and vitamin D—in regulating calcium homeostasis. These three hormones, as well as several other endocrine factors, are all involved in controlling calcium levels for various physiologic needs. How these hormones interact in controlling normal bone formation and resorption is of particular interest to rehabilitation specialists. Regulation of bone mineral homeostasis and the principal hormones involved in this process are presented in the following section. 

These polymer-coated liposomes showed high potency in oral delivery of peptide drugs such as insulin and calcitonin, mainly because of the mucoadhe-sion of the chitosan-coated liposomes to the intestinal tract (Takeuchi et al. 1996, 2001,2003,2005a). Similar trials have been reported by Guo et al. (2003), who investigated the effect of chitosan concentration and lipid type on the characteristics of chitosan-coated liposomes and their interactions with leupro-lide. They found that a thicker adsorptive layer could be realized by using low... 

Vitamin D, along with parathyroid hormone and calcitonin, plays a primary role in calcium and phosphorus homeostasis in the body. Intensive research efforts over the past several years have elucidated a role for vitamin D in many other physiological processes as well. The biological actions of this seco-steroid are mediated primarily through the action of its polar metabolite, 1,25-dihydroxy vitamin D3 (l,25(OH)2D3). There is emerging evidence that l,25(OH)2D3 has many more target tissues than those involved in its classical role in the control of mineral metabolism. In addition, some of the actions of l,25(OH)2D3 may be mediated by mechanisms other than the classical steroid-receptor interaction. In this chapter we will provide a brief overview of the multiple actions of vitamin D3 and the pleiotropic mechanisms by which these actions are accomplished. 

The fact that vitamin D3 toxicity results from primarily uncontrolled intestinal calcium absorption suggests that it is dietary calcium and not vitamin D3 that exacerbates the hypervitaminosis D3 toxicity effect [119]. This was tested by the interaction of excess vitamin D3 and calcium restriction [113]. Rats fed a calcium-deficient diet and given 25,000 IU of vitamin D3 three dmes/week for 2.5 weeks did not succumb to overt hypervitaminosis D3. Simple calcium restriction increased intestinal but not renal 24-OHase activity, presumably because of the absence of parathyroid hormone regulation in the intestine [113]. Coupled with vitamin D3, excess intestinal 24-OHase increased several fold more. However, when dietary calcium was adequate, vitamin D3 excess increased intestinal 24-OHase activity only slightly because of a suppressive mechanism regulated in part by increased blood calcitonin [120],... 

On July 10, 2006, Nastech was notified by the FDA that its ANDA for intranasal calcitonin salmon was not approvable at present based on concerns relating to the potential for immunogenicity that might result from a possible interaction between calcitonin salmon and chlorobutanol, the preservative in the formulation. 

Smullin DH, Skilling SR, Larson AA (1990) Interactions between substance P, calcitonin gene-related peptide, taurine and excitatory amino-acids in the spinal cord. Pain 42 93-101... 

Interaction with phospholipid bilayers of a number of hormones, such as atriopeptin HI, an atrial natriuretic peptide, and of calcitonin was investigated by Surewicz et al. 

Surewicz et al., 1987a, b). FTIR shows that below Tm, calcitonin decreases the conformational order of the acyl chains of DMPG and DMPA. However, the interaction with DMPA is weaker, due to the difference in the degree of intermolecular interaction between the headgroups of the two lipids. 

Calcitonin, a peptide hormone of 32 amino acids having a regulatory function in calcium and phosphoms metabolism, is used in various bone disorders such as osteoporosis. Salmon, human, pig and eel calcitonin are used therapeutically. Species differences may be significant - salmon calcitonin is ten times more potent than human calcitonin, for example. Human calcitonin (hCT) has a tendency to associate rapidly in solution and, like insulin, form fibrils, resulting in a viscous solution. The fibrils are 8 nm in diameter and often associate with one another. Heating fibrillated hCT solutions in 50% acetic acid-water converts the system back to soluble monomers. hCT has a pK of 8.7, while salmon calcitonin (SCT) has a pK of 10.4. This accounts for the high stability of SCT at pH 7.4, as electrostatic interactions between calcitonin monomers play a role. At pH 7.4, SCT monomers will be charged and will repel each other. At 20 mg moH in Tris buffer at 22°C and pH 7.4 the fibrillation time for hCT is 1 minute, whereas for SCT it is of the order of 21 days. 

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