Dual regulation of L-type Ca2+ channels by serotonin 2 receptor stimulation in vascular smooth muscle cells.
The purpose of the present study was to investigate regulation of voltage-dependent Ca2+ channels by serotonin in rat aortic smooth muscle cells in primary culture. L- and T-type Ca2+ currents (ICa) were recorded using the whole cell voltage-clamp method. Without pretreatment, in 25 of 30 cells examined, 10 microM serotonin decreased L-type ICa to various extents (-14 to -72%). However, in the remaining five cells, serotonin increased L-type ICa 21 +/- 4%. Thus, in 30 cells, serotonin decreased L-type ICa an average of 22 +/- 5%. In the presence of intracellular heparin (100 micrograms/ml), a blocker of inositol 1,4,5-trisphosphate binding to its receptor, serotonin increased L-type ICa in all cells 29 +/- 3% (n = 6). When stored Ca2+ was depleted by pretreatment either with 20 microM ryanodine and 20 mM caffeine or with 100 nM A-23187, serotonin also increased L-type ICa in all cells 30 +/- 5 (n = 4) or 37 +/- 5% (n = 12), respectively. In the presence of heparin, the serotonin-induced increase of L-type ICa was prevented by 100 nM staurosporine (2 +/- 3%; n = 6, P < 0.01). The serotonin-induced decrease of L-type ICa was significantly augmented by 100 nM staurosporine (-43 +/- 10%; n = 5). Phorbol 12,13-dibutylate (PDBu; 1 microM) increased L-type ICa 29 +/- 3% (n = 6), and serotonin did not further increase L-type ICa after its potentiation by PDBu.(ABSTRACT TRUNCATED AT 250 WORDS)
Hirakawa
Y
Y
Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kuga
T
T
Kobayashi
S
S
Kanaide
H
H
Takeshita
A
A
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000145:classification / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology
D015220:Calcium Channels; D011985:Receptors, Serotonin; D012701:Serotonin; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C