Role of sarcoplasmic reticulum in the contractile function of vascular smooth muscle as studied by 2,5-di-(tert-butyl)-1,4-benzohydroquinone.
The effects of 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), a potent selective inhibitor of hepatocyte endoplasmic reticulum Ca(2+)-ATPase, were functionally examined in rat aorta in order to assess whether tBuBHQ also acts as a Ca2+ pump inhibitor of sarcoplasmic reticulum (SR) in vascular smooth muscle. tBuBHQ elicited a slowly developing and gradually decreasing contraction which was dependent on extracellular Ca2+. We utilize the phenylephrine (PE)-induced transient contractile response in Ca(2+)-free medium as an indirect index on the status of intracellular Ca2+ store. When preparations, depleted of their PE-sensitive Ca2+ store, were allowed to replete their stores in Ca(2+)-containing medium, a sustained contraction in tBuBHQ-treated preparations was observed, whereas in untreated control preparations, readministration of Ca2+ elicited no contraction, or occasionally a weak, transient contraction. In control tissues, subsequent application of PE in Ca(2+)-free medium after Ca2+ loading resulted in full restoration of the transient contraction to PE; but such a transient contraction was not observed in the presence of tBuBHQ. These results indicated that the sequestration of Ca2+ into the PE-sensitive pool was inhibited by tBuBHQ. We also assessed effects of tBuBHQ on phentolamine-induced relaxation in PE-precontracted tissues in Ca(2+)-containing medium. A slower rate of relaxation was observed in preparations treated with tBuBHQ. In conclusion, our findings are consistent with the hypothesis that tBuBHQ acts as a SR Ca2+ pump inhibitor, interfering with effective refilling of PE-sensitive intracellular Ca2+ stores.
Shimamoto
H
H
Department of Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Majarais
I L
IL
Shimamoto
Y
Y
Kwan
C Y
CY
Daniel
E E
EE
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D006873:Hydroquinones / Q000494:pharmacology*; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors
D000975:Antioxidants; D006873:Hydroquinones; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D010656:Phenylephrine; C019359:2,5-di-tert-butylhydroquinone; D000252:Calcium-Transporting ATPases; D002118:Calcium; D010646:Phentolamine