Amylin-amide, TFA( human)

Amylin‑amide (CAS No.: 122384-88-7) is a polypeptide synthesized and secreted by pancreatic β cells. It belongs to the calcitonin multigene family and has high sequence homology with calcitonin gene-related peptide (CGRP), with multiple biological functions including inhibition of bone resorption, reduction of blood calcium, promotion of endothelial cell proliferation, and upregulation of intracellular cAMP in uterine smooth muscle cells. It can directly act on osteoclasts to inhibit bone resorption activity, and can also act as an agonist to activate CGRP₁ receptors on uterine smooth muscle cells (Gαs-coupled seven-transmembrane receptors; the corresponding effect can be antagonized by CGRP₈₋₃₇), mainly involving bone metabolism regulatory pathways, the Gαs–adenylyl cyclase–cAMP signaling pathway, and pathways related to endothelial cell proliferation.

In cell-level experiments, amylin‑amide showed strong inhibitory activity against bone resorption in rat primary osteoclast bone resorption assays, with an ED₅₀ for inhibition of bone resorption of approximately 1300 pM and a potency of about 1/33 that of human calcitonin; in human uterine smooth muscle cells, treatment with 500 nM amylin‑amide combined with 1 mM IBMX for 15 min increased intracellular cAMP levels by approximately 2.3-fold compared with IBMX alone, but its potency was significantly lower than that of CGRP (5 nM was sufficient to produce a significant increase); in human umbilical vein endothelial cells, amylin‑amide promoted proliferation in a concentration-dependent manner at 1–10 nM, with 10 nM increasing cell number by approximately 56%±14% and 1 nM increasing DNA synthesis by approximately 24%, while the proliferative effect decreased slightly above the optimal concentration. Common cell experiment applications include: rat primary osteoclast bone resorption assays (0.025–25 nM, with 25 nM completely inhibiting bone resorption pit formation without affecting osteoclast number or viability), human umbilical vein endothelial cell proliferation and DNA synthesis assays (0.1–100 nM), and human uterine smooth muscle cell cAMP detection assays (approximately 500 nM).

At the animal level, amylin‑amide is mainly used to evaluate its physiological activity on calcium homeostasis and bone metabolism. In hypocalcemic experiments performed by tail vein injection in male Wistar rats of about 50 g, its ED₅₀ was approximately 35 pmol/animal, with a potency of about 1/44 that of human calcitonin (95% confidence interval 22–66); after tail vein injection at a dose of 30 pmol/animal, blood calcium levels were significantly reduced within 15–30 min, and the effect lasted for about 90 min. The overall time course of action was similar to that of human calcitonin, suggesting that it has strong acute hypocalcemic and bone resorption-inhibiting activity in vivo.

Overall, amylin‑amide is considered one of the most potent non-calcitonin hypocalcemic polypeptides known to date. Physiologically, it may play an important regulatory role in the maintenance of bone mass and the targeted transport of postprandial dietary calcium to bone, and has certain research value in metabolic endocrinology and bone metabolism.

References:

[1] Zaidi M, Datta HK, Bevis PJ, Wimalawansa SJ, MacIntyre I. Amylin-amide: a new bone-conserving peptide from the pancreas. Exp Physiol. 1990 Jul;75(4):529-36. doi: 10.1113/expphysiol.1990.sp003429. PMID: 2223054.

[2] Datta H, Rafter P, Chen Z, Wimalawansa S, Macintyre I. Amylin-amide displays a proliferative effect on human umbilical vein endothelial cells. Biochem Soc Trans. 1990 Dec;18(6):1276. doi: 10.1042/bst0181276. PMID: 2088915.

[3] Casey ML, Smith J, Alsabrook G, MacDonald PC. Activation of adenylyl cyclase in human myometrial smooth muscle cells by neuropeptides. J Clin Endocrinol Metab. 1997 Sep;82(9):3087-92. doi: 10.1210/jcem.82.9.4244. PMID: 9284749.