Sustained norepinephrine contraction in the rat portal vein is lost when Ca(2+) is replaced with Sr(2+).
Agonist-induced activation of smooth muscle involves a rise in intracellular Ca(2+) concentration and sensitization of myosin light chain phosphorylation to Ca(2+). Sr(2+) can enter through Ca(2+) channels, be sequestered and released from sarcoplasmic reticulum, and replace Ca(2+) in activation of myosin light chain phosphorylation. Sr(2+) cannot replace Ca(2+) in facilitation of agonist-activated Ca(2+)-dependent nonselective cation channels. It is not known whether Sr(2+) can replace Ca(2+) in small G protein-mediated sensitization of phosphorylation. To explore mechanisms involved in alpha-receptor-activated contractions in smooth muscle, effects of replacing Ca(2+) with Sr(2+) were examined in rat portal vein. Norepinephrine (NE) at >3.0 x 10(-7) M in the presence of Ca(2+) resulted in a strong sustained contraction, whereas this sustained component was absent in the presence of Sr(2+); only the amplitude of phasic contractions increased. Pretreatment with low (approximately 0.05 mM) free Ca(2+) followed by 2.5 mM Sr(2+) resulted in a sustained component of the NE response. In beta-escin-permeabilized preparations, phenylephrine in the presence of GTP or guanosine 5'-O-(3-thiotriphosphate) alone induced sensitization to Sr(2+). In conclusion, a Ca(2+)-regulated membrane/channel process is required for the sustained component of NE responses in rat portal vein. Sensitization alone is not responsible for the sustained phase of the NE contraction.
Bonnevier
Johan
J
Department of Physiological Sciences, Lund University, Tornavägen 10, SE-221 Lund, Sweden.
Malmqvist
Ulf
U
Sonntag
Dagmar
D
Schroeter
Mechthild
M
Nilsson
Holger
H
Pfitzer
Gabriele
G
Arner
Anders
A
D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics*; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D011169:Portal Vein / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013324:Strontium / Q000493:pharmacokinetics*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; D013324:Strontium