Insulin preincubation effects on rat vessel contractile responses: role of the sarcoplasmic reticulum.
In the present work, we studied the possible mechanisms involved in the insulin-induced acceleration of ET1 contractions. We observed a shortening of the half-life needed to achieve maximal developed force (t(1/2)) at 10(-7) M ET1 in rat aortic rings preincubated for 120 min with 3 nM insulin (control 380 +/- 15 s vs. 319 +/- 8 s with insulin, n = 28, p < 0.05). A tyrosine kinase linked receptor was involved in this effect because it was abolished by 30 microM genistein. Endothelium denudation and 10 microM indomethacin treatment did not effect this insulin effect, suggesting its independence of endothelial-derived factors. The effect was still present when the only source of Ca2+ was intracellular (t(1/2) values in the absence of external Ca2+: control 467 +/- 68 s vs. 213 +/- 28 s with insulin, n = 16, p < 0.05), but was blunted if the sarcoplasmic reticulum (SR) Ca2+ source was suppressed by exposure to 10 microM thapsigargin or 10 microM ryanodine. Preincubation with insulin did not potentiate either SR 45Ca2+ uptake or contractions evoked by caffeine-sensitive SR Ca2+ release. Since 30 microM cheleritrine abolished insulin-induced acceleration of ET1 contractions, we propose that the hormone might enhance a signal pathway related to PKC in order to produce a faster Ca2+ release from the SR.
Rebolledo
A
A
Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Argentina. ar@nahuel.biol.unlp.edu.ar
Milesi
V
V
Raingo
J
J
Gómez Alvis
A
A
Rinaldi
G J
GJ
Grassi de Gende
A O
AO
D000818:Animals; D001011:Aorta; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006946:Hyperinsulinism; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007328:Insulin; D002110:Caffeine; D011493:Protein Kinase C; D002118:Calcium