Premium
Ghrelin signalling in guinea‐pig femoral artery smooth muscle cells
Author(s) -
Mladenov M. I.,
Hristov K. L.,
Dimitriova D. Z.,
Schubert R.,
Lubomirov L. T.,
Gjorgoski I. K.,
Duridanova D. B.,
Gagov H. S.
Publication year - 2008
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2008.01880.x
Subject(s) - iberiotoxin , medicine , endocrinology , ghrelin , myograph , carbachol , chemistry , apamin , protein kinase a , potassium channel , artery , receptor , kinase , biochemistry
Aim: Our aim was to study the new signalling pathway of ghrelin in the guinea‐pig femoral artery using the outward I K as a sensor. Methods: Whole‐cell patch‐clamp experiments were performed on single smooth muscle cells, freshly isolated from the guinea‐pig femoral artery. The contractile force of isometric preparations of the same artery was measured using a wire‐myograph. Results: In a Ca 2+ ‐ and nicardipine‐containing external solution, 1 mmol L −1 tetraethylammonium reduced the net I K by 49 ± 7%. This effect was similar and not additive to the effect of the specific BK Ca channel inhibitor iberiotoxin. Ghrelin (10 −7 mol L −1 ) quickly and significantly reduced the amplitudes of tetraethylammonium‐ and iberiotoxin‐sensitive currents through BK Ca channels. The application of 5 × 10 −6 mol L −1 desacyl ghrelin did not affect the amplitude of the control I K but it successfully prevented the ghrelin‐induced I K decrease. The effect of ghrelin on I K was insensitive to selective inhibitors of cAMP‐dependent protein kinase, soluble guanylyl cyclase, cGMP‐dependent protein kinase or a calmodulin antagonist, but was effectively antagonized by blockers of BK Ca channels, phosphatidylinositol‐phospholipase C, phosphatidylcholine‐phospholipase C, protein kinase C, SERCA, IP 3 ‐induced Ca 2+ release and by pertussis toxin. The ghrelin‐induced increase in the force of contractions was blocked when iberiotoxin (10 −7 mol L −1 ) was present in the bath solution. Conclusions: Ghrelin reduces I K(Ca) in femoral artery myocytes by a mechanism that requires activation of Gα i/o ‐proteins, phosphatidylinositol phospholipase C, phosphatidylcholine phospholipase C, protein kinase C and IP 3 ‐induced Ca 2+ release.