Serotonin-induced Na+/K+ pump stimulation in vascular smooth muscle cells. Evidence for coupling to multiple receptor mechanisms.
Exposure of cultured canine femoral artery vascular smooth muscle cells to serotonin (5-HT) caused a 3.6-fold stimulation of ouabain-sensitive 86Rb uptake. The 5-HT2 receptor antagonist, ketanserin, partly blocked the 5-HT-mediated Na+/K+ pump stimulation and the 5-HT1/5-HT2 receptor antagonist, methiothepin, completely blocked the response, suggesting that both 5-HT1 and 5-HT2 receptors play a role in the 5-HT-mediated Na+/K+ pump activation. Second messengers generated by 5-HT2 receptor-mediated phosphoinositide hydrolysis, Ins(1,4,5)P3 and diacylglycerol were implicated in the stimulatory action of 5-HT on the vascular Na+/K+ pump. Like some other contractile agonists, 5-HT activated a Na+ influx pathway which caused Na+/K+ pump stimulation by increasing the rate-limiting substrate. The maximum stimulation of Na+ influx by 5-HT was 2.5-fold. The 5-HT-stimulated Na+ influx was totally blocked by methiothepin but only 29% inhibited by ketanserin, indicating that most of the Na+ influx was mediated by the 5-HT1 receptor. The 5-HT-stimulated Na+ influx was substantially inhibited by 50 microM dimethylamiloride, suggesting that the Na+ influx pathway stimulated by 5-HT was Na+/H+ exchange. BAPTA/AM 1,2-[bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetra (acetoxymethyl) ester], an intracellular Ca++ chelator, partly blocked 5-HT-stimulated Na+ influx and ouabain-sensitive 86Rb uptake, suggesting that Ca++ is an important mediator of these responses. These data suggest that: 1) 5-HT, in addition to its well known activity as a contractile agonist, can stimulate the electrogenic Na+/K+ pump which, in theory, would tend to oppose contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Navran
S S
SS
Department of Medicine, Baylor College of Medicine, Houston, Texas.
Allain
G
G
Garcia
H F
HF
Allen
J C
JC
Seidel
C L
CL
D000818:Animals; D001693:Biological Transport, Active; D004285:Dogs; D005263:Femoral Artery / Q000166:cytology / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000145:classification / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D013268:Stimulation, Chemical
D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D012701:Serotonin; D012964:Sodium; D011188:Potassium