International Union of Basic and Clinical Pharmacology. XCIII. The Parathyroid Hormone Receptors—Family B G Protein–Coupled Receptors

Gardella, Thomas J.; Vilardaga, Jean-Pierre

doi:10.1124/pr.114.009464

Cited by 95 publications

(108 citation statements)

References 300 publications

(330 reference statements)

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“…The molecular basis in terms of specific interactions of ligands with PTHR1 and the post-binding events triggering downstream signals controlling entirely different functions needs further exploration (Cheloha et al, 2015;Gardella and Vilardaga, 2015). In comparison to synthetic hPTH 3-34 (human PTH), hPTH 1-34 was reported to significantly stimulate lipolysis in human adipose tissue, indicating that amino acids at positions 1 (serine) and 2 (valine) are crucial for the lipolytic action of PTH.…”

Section: Parathyroid Hormonementioning

confidence: 99%

Non-adrenergic control of lipolysis and thermogenesis in adipose tissues

Braun

Oeckl

Westermeier

et al. 2018

Journal of Experimental Biology

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The enormous plasticity of adipose tissues, to rapidly adapt to altered physiological states of energy demand, is under neuronal and endocrine control. In energy balance, lipolysis of triacylglycerols and re-esterification of free fatty acids are opposing processes operating in parallel at identical rates, thus allowing a more dynamic transition from anabolism to catabolism, and vice versa. In response to alterations in the state of energy balance, one of the two processes predominates, enabling the efficient mobilization or storage of energy in a negative or positive energy balance, respectively. The release of noradrenaline from the sympathetic nervous system activates lipolysis in a depot-specific manner by initiating the canonical adrenergic receptor-G s -protein-adenylyl cyclase-cyclic adenosine monophosphate-protein kinase A pathway, targeting proteins of the lipolytic machinery associated with the interface of the lipid droplets. In brown and brite adipocytes, lipolysis stimulated by this signaling pathway is a prerequisite for the activation of non-shivering thermogenesis. Free fatty acids released by lipolysis are direct activators of uncoupling protein 1-mediated leak respiration. Thus, pro-and anti-lipolytic mediators are bona fide modulators of thermogenesis in brown and brite adipocytes. In this Review, we discuss adrenergic and non-adrenergic mechanisms controlling lipolysis and thermogenesis and provide a comprehensive overview of pro-and anti-lipolytic mediators.

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Section: Parathyroid Hormonementioning

confidence: 99%

Non-adrenergic control of lipolysis and thermogenesis in adipose tissues

Braun

Oeckl

Westermeier

et al. 2018

Journal of Experimental Biology

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“…33 PTHR1 agonists are of interest clinically as they can promote bone growth with continued daily administration. 34, 35 Determining whether new analogues of PTHR1 agonist peptides can induce the acute calcemic response in mice serves as a readily accessible initial test of in vivo activity and is well-suited for assessing several candidate compounds in parallel for the prospect of subsequent longer-term evaluation.…”

Section: Introductionmentioning

confidence: 99%

Development of Potent, Protease-Resistant Agonists of the Parathyroid Hormone Receptor with Broad β Residue Distribution

et al. 2017

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The parathyroid hormone receptor-1 (PTHR1) is a member of the B-family of GPCRs; these receptors are activated by long polypeptide hormones and constitute targets of drug development efforts. Parathyroid hormone (PTH; 84 residues) and PTH-related protein (PTHrP; 141 residues) are natural agonists of PTHR1, and an N-terminal fragment of PTH, PTH(1−34), is used clinically to treat osteoporosis. Conventional peptides in the 20-40-mer length range are rapidly degraded by proteases, which may limit their biomedical utility. We have used the PTHR1-ligand system to explore the impact of broadly distributed replacement of α-amino acid residues with β-amino acid residues on susceptibility to proteolysis and agonist activity. This effort led us to identify new PTHR1 agonists that contain α→β replacements throughout their sequences, manifest potent agonist activity in cellular assays, and display remarkable resistance to proteolysis. The strategy we have employed suggests a path toward identifying protease-resistant agonists of other B-family GPCRs.

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“…The PTH receptor (PPR) is mainly expressed in bone and kidney, but its expression has also been reported in other tissues where it likely reflects the local paracrine role of PTH related protein [5][6][7]. In bone, PPR is expressed in osteoclasts [8] and mainly in cells of osteoblastic lineage as osteocytes [9].…”

Section: Introductionmentioning

confidence: 99%

Treatment with intermittent PTH increases Wnt10b production by T cells in osteoporotic patients

et al. 2015

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Abstract.Purpose. The aim of this study is to assess the effect of PTH on Wnt10b production by immune system cells in humans. We assessed both the effect of intermittent PTH administration (iPTH) and of chronic PTH hyper secretion in primary hyperparathyroidism (PHP).Methods. Eighty-two women affected by post-menopausal osteoporosis were randomly assigned to treatment with calcium and vitamin D alone (22) The effect of chronic elevation of PTH was evaluated in 20 patients affected by PHP at diagnosis and after surgical removal of parathyroid adenoma.WNT10b from both osteoporotic and PHP patients was compared to healthy subjects matched for age and sex.Results. iPTH increases Wnt10b production by T cells, whereas PHP does not. After surgical restoration of normal parathyroid function, WNT10b decreases, although it is still comparable with healthy subjects level. Thus chronic elevation of PTH does not significantly increase WNT10b production as respect to control.Conclusions. This is the first work showing the effect of both intermittent and chronic PTH increase on Wnt10b production by immune system cells. We suggest that, in humans, T cells amplified the anabolic effect of PTH on bone, by increasing Wnt10b production, which stimulates osteoblast activity.Key words: osteoporosis, primary hyperparathyroidism, PTH, Wnt10b, T cells, immune system. Mini Abstract.We evaluated the effect of PTH on Wnt10b production by immune system cells in humans.We showed that bone anabolic effect of intermittent PTH treatment may be amplified by T cells through increased production of Wnt10b. Chronic increase in PTH as in primary hyperparathyroidism does not increase Wnt10b expression. INTRODUCTION.

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International Union of Basic and Clinical Pharmacology. XCIII. The Parathyroid Hormone Receptors—Family B G Protein–Coupled Receptors

Cited by 95 publications

References 300 publications

Non-adrenergic control of lipolysis and thermogenesis in adipose tissues

Non-adrenergic control of lipolysis and thermogenesis in adipose tissues

Development of Potent, Protease-Resistant Agonists of the Parathyroid Hormone Receptor with Broad β Residue Distribution

Treatment with intermittent PTH increases Wnt10b production by T cells in osteoporotic patients

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