Calcium sensing receptor in developing human airway smooth muscle

Anne M. Roesler; Sarah A. Wicher; Jovanka Ravix; Rodney D. Britt; Logan Manlove; Jacob J. Teske; Katelyn Cummings; Michael A. Thompson; Carol Farver; Peter MacFarlane; Christina M. Pabelick; Y. S. Prakash

doi:10.1002/jcp.28115

Calcium sensing receptor in developing human airway smooth muscle

Anne M. Roesler, Sarah A. Wicher, Jovanka Ravix, Rodney D. Britt, Logan Manlove, Jacob J. Teske, Katelyn Cummings, Michael A. Thompson, Carol Farver, Peter MacFarlane, Christina M. Pabelick, Y. S. Prakash

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Airway smooth muscle (ASM) regulation of airway structure and contractility is critical in fetal/neonatal physiology in health and disease. Fetal lungs experience higher Ca ²⁺ environment that may impact extracellular Ca ²⁺ ([Ca ²⁺ ] _o ) sensing receptor (CaSR). Well-known in the parathyroid gland, CaSR is also expressed in late embryonic lung mesenchyme. Using cells from 18-22 week human fetal lungs, we tested the hypothesis that CaSR regulates intracellular Ca ²⁺ ([Ca ²⁺ ] _i ) in fetal ASM (fASM). Compared with adult ASM, CaSR expression was higher in fASM, while fluorescence Ca ²⁺ imaging showed that [Ca ²⁺ ] _i was more sensitive to altered [Ca ²⁺ ] _o . The fASM [Ca ²⁺ ] _i responses to histamine were also more sensitive to [Ca ²⁺ ] _o (0–2 mM) compared with an adult, enhanced by calcimimetic R568 but blunted by calcilytic NPS2143. [Ca ²⁺ ] _i was enhanced by endogenous CaSR agonist spermine (again higher sensitivity compared with adult). Inhibition of phospholipase C (U73122; siRNA) or inositol 1,4,5-triphosphate receptor (Xestospongin C) blunted [Ca ²⁺ ] _o sensitivity and R568 effects. NPS2143 potentiated U73122 effects. Store-operated Ca ²⁺ entry was potentiated by R568. Traction force microscopy showed responsiveness of fASM cellular contractility to [Ca ²⁺ ] _o and NPS2143. Separately, fASM proliferation showed sensitivity to [Ca ²⁺ ] _o and NPS2143. These results demonstrate functional CaSR in developing ASM that modulates airway contractility and proliferation.

Original language	English (US)
Pages (from-to)	14187-14197
Number of pages	11
Journal	Journal of Cellular Physiology
Volume	234
Issue number	8
DOIs	https://doi.org/10.1002/jcp.28115
State	Published - Aug 2019

Keywords

calcium
class C GPCR
contraction
fetal
lung
proliferation

ASJC Scopus subject areas

Physiology
Clinical Biochemistry
Cell Biology

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10.1002/jcp.28115

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@article{3c5204b63c64446a93978a6cda7b9db0,

title = "Calcium sensing receptor in developing human airway smooth muscle",

abstract = " Airway smooth muscle (ASM) regulation of airway structure and contractility is critical in fetal/neonatal physiology in health and disease. Fetal lungs experience higher Ca 2+ environment that may impact extracellular Ca 2+ ([Ca 2+ ] o ) sensing receptor (CaSR). Well-known in the parathyroid gland, CaSR is also expressed in late embryonic lung mesenchyme. Using cells from 18-22 week human fetal lungs, we tested the hypothesis that CaSR regulates intracellular Ca 2+ ([Ca 2+ ] i ) in fetal ASM (fASM). Compared with adult ASM, CaSR expression was higher in fASM, while fluorescence Ca 2+ imaging showed that [Ca 2+ ] i was more sensitive to altered [Ca 2+ ] o . The fASM [Ca 2+ ] i responses to histamine were also more sensitive to [Ca 2+ ] o (0–2 mM) compared with an adult, enhanced by calcimimetic R568 but blunted by calcilytic NPS2143. [Ca 2+ ] i was enhanced by endogenous CaSR agonist spermine (again higher sensitivity compared with adult). Inhibition of phospholipase C (U73122; siRNA) or inositol 1,4,5-triphosphate receptor (Xestospongin C) blunted [Ca 2+ ] o sensitivity and R568 effects. NPS2143 potentiated U73122 effects. Store-operated Ca 2+ entry was potentiated by R568. Traction force microscopy showed responsiveness of fASM cellular contractility to [Ca 2+ ] o and NPS2143. Separately, fASM proliferation showed sensitivity to [Ca 2+ ] o and NPS2143. These results demonstrate functional CaSR in developing ASM that modulates airway contractility and proliferation.",

keywords = "calcium, class C GPCR, contraction, fetal, lung, proliferation",

author = "Roesler, {Anne M.} and Wicher, {Sarah A.} and Jovanka Ravix and Britt, {Rodney D.} and Logan Manlove and Teske, {Jacob J.} and Katelyn Cummings and Thompson, {Michael A.} and Carol Farver and Peter MacFarlane and Pabelick, {Christina M.} and Prakash, {Y. S.}",

note = "Publisher Copyright: {\textcopyright} 2019 Wiley Periodicals, Inc.",

year = "2019",

month = aug,

doi = "10.1002/jcp.28115",

language = "English (US)",

volume = "234",

pages = "14187--14197",

journal = "Journal of Cellular Physiology",

issn = "0021-9541",

publisher = "Wiley-Liss Inc.",

number = "8",

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TY - JOUR

T1 - Calcium sensing receptor in developing human airway smooth muscle

AU - Roesler, Anne M.

AU - Wicher, Sarah A.

AU - Ravix, Jovanka

AU - Britt, Rodney D.

AU - Manlove, Logan

AU - Teske, Jacob J.

AU - Cummings, Katelyn

AU - Thompson, Michael A.

AU - Farver, Carol

AU - MacFarlane, Peter

AU - Pabelick, Christina M.

AU - Prakash, Y. S.

PY - 2019/8

Y1 - 2019/8

N2 - Airway smooth muscle (ASM) regulation of airway structure and contractility is critical in fetal/neonatal physiology in health and disease. Fetal lungs experience higher Ca 2+ environment that may impact extracellular Ca 2+ ([Ca 2+ ] o ) sensing receptor (CaSR). Well-known in the parathyroid gland, CaSR is also expressed in late embryonic lung mesenchyme. Using cells from 18-22 week human fetal lungs, we tested the hypothesis that CaSR regulates intracellular Ca 2+ ([Ca 2+ ] i ) in fetal ASM (fASM). Compared with adult ASM, CaSR expression was higher in fASM, while fluorescence Ca 2+ imaging showed that [Ca 2+ ] i was more sensitive to altered [Ca 2+ ] o . The fASM [Ca 2+ ] i responses to histamine were also more sensitive to [Ca 2+ ] o (0–2 mM) compared with an adult, enhanced by calcimimetic R568 but blunted by calcilytic NPS2143. [Ca 2+ ] i was enhanced by endogenous CaSR agonist spermine (again higher sensitivity compared with adult). Inhibition of phospholipase C (U73122; siRNA) or inositol 1,4,5-triphosphate receptor (Xestospongin C) blunted [Ca 2+ ] o sensitivity and R568 effects. NPS2143 potentiated U73122 effects. Store-operated Ca 2+ entry was potentiated by R568. Traction force microscopy showed responsiveness of fASM cellular contractility to [Ca 2+ ] o and NPS2143. Separately, fASM proliferation showed sensitivity to [Ca 2+ ] o and NPS2143. These results demonstrate functional CaSR in developing ASM that modulates airway contractility and proliferation.

AB - Airway smooth muscle (ASM) regulation of airway structure and contractility is critical in fetal/neonatal physiology in health and disease. Fetal lungs experience higher Ca 2+ environment that may impact extracellular Ca 2+ ([Ca 2+ ] o ) sensing receptor (CaSR). Well-known in the parathyroid gland, CaSR is also expressed in late embryonic lung mesenchyme. Using cells from 18-22 week human fetal lungs, we tested the hypothesis that CaSR regulates intracellular Ca 2+ ([Ca 2+ ] i ) in fetal ASM (fASM). Compared with adult ASM, CaSR expression was higher in fASM, while fluorescence Ca 2+ imaging showed that [Ca 2+ ] i was more sensitive to altered [Ca 2+ ] o . The fASM [Ca 2+ ] i responses to histamine were also more sensitive to [Ca 2+ ] o (0–2 mM) compared with an adult, enhanced by calcimimetic R568 but blunted by calcilytic NPS2143. [Ca 2+ ] i was enhanced by endogenous CaSR agonist spermine (again higher sensitivity compared with adult). Inhibition of phospholipase C (U73122; siRNA) or inositol 1,4,5-triphosphate receptor (Xestospongin C) blunted [Ca 2+ ] o sensitivity and R568 effects. NPS2143 potentiated U73122 effects. Store-operated Ca 2+ entry was potentiated by R568. Traction force microscopy showed responsiveness of fASM cellular contractility to [Ca 2+ ] o and NPS2143. Separately, fASM proliferation showed sensitivity to [Ca 2+ ] o and NPS2143. These results demonstrate functional CaSR in developing ASM that modulates airway contractility and proliferation.

KW - calcium

KW - class C GPCR

KW - contraction

KW - fetal

KW - lung

KW - proliferation

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DO - 10.1002/jcp.28115

M3 - Article

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AN - SCOPUS:85059688453

SN - 0021-9541

VL - 234

SP - 14187

EP - 14197

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

IS - 8

ER -

Calcium sensing receptor in developing human airway smooth muscle

Abstract

Keywords

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