TY - JOUR
T1 - Ligand-dependent activation of the melanocortin 5 receptor
T2 - cAMP production and ryanodine receptor-dependent elevations of [Ca2+]i
AU - Hoogduijn, M. J.
AU - McGurk, S.
AU - Ancans, J.
AU - Thody, A. J.
AU - Smit, N. P.M.
AU - Nibbering, P. H.
AU - van der Laarse, A.
PY - 2002
Y1 - 2002
N2 - The melanocortins are involved in the regulation of various cognitive and physiological processes such as learning, feeding, immune suppression, pigmentation, and sebum production. Five melanocortin receptors have been identified, of which the melanocortin 5 receptor (MC5R) has the most widespread distribution. This subtype is found in the brain, and at numerous peripheral sites including the skin where it is expressed in the sebaceous glands. The purpose of this study was to identify the peptide that functions as a natural ligand at the MC5R in the skin. α-MSH, ACTH1-39, ACTH1-17, ACTH1-10, and ACTH4-10 all increased the production of cAMP in HEK293 cells transfected with the mouse MC5R. α-MSH and ACTH1-17 were the most potent in this respect. In addition, all peptides stimulated a rapid and transient increase in [Ca2+]i, and, ACTH1-10 was the most potent. The increases in [Ca2+]i were of intracellular origin, but not associated with inositol phosphate production. The elevations in [Ca2+]i were reduced by ruthenium red and procaine and it is therefore possible that they were mediated via ryanodine receptors.
AB - The melanocortins are involved in the regulation of various cognitive and physiological processes such as learning, feeding, immune suppression, pigmentation, and sebum production. Five melanocortin receptors have been identified, of which the melanocortin 5 receptor (MC5R) has the most widespread distribution. This subtype is found in the brain, and at numerous peripheral sites including the skin where it is expressed in the sebaceous glands. The purpose of this study was to identify the peptide that functions as a natural ligand at the MC5R in the skin. α-MSH, ACTH1-39, ACTH1-17, ACTH1-10, and ACTH4-10 all increased the production of cAMP in HEK293 cells transfected with the mouse MC5R. α-MSH and ACTH1-17 were the most potent in this respect. In addition, all peptides stimulated a rapid and transient increase in [Ca2+]i, and, ACTH1-10 was the most potent. The increases in [Ca2+]i were of intracellular origin, but not associated with inositol phosphate production. The elevations in [Ca2+]i were reduced by ruthenium red and procaine and it is therefore possible that they were mediated via ryanodine receptors.
UR - http://www.scopus.com/inward/record.url?scp=0036296115&partnerID=8YFLogxK
U2 - 10.1006/bbrc.2001.6283
DO - 10.1006/bbrc.2001.6283
M3 - Article
C2 - 11785979
AN - SCOPUS:0036296115
SN - 0006-291X
VL - 290
SP - 844
EP - 850
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -