Comparison of the effects of thapsigargin and BAY K 8644 on spontaneous mechanical activity in rat portal vein and contractile responses of rat cardiac muscle.
The effect of thapsigargin, 10(-9)-10(-6) M, and Bay K 8644, 10(-9)-10(-7) M, was studied on isolated portal veins and cardiac muscles from rats. In rat portal veins thapsigargin induced a concentration dependent increase in the amplitude of the spontaneous mechanical activity without increasing the frequency of spontaneous activity. Thapsigargin was less effective than Bay K 8644 in increasing the amplitude of the mechanical activity. In contrast to thapsigargin Bay K 8644, 10(-6) M increases the frequency of the mechanical activity. Atropine, 10(-6) M, and phentolamine, 10(-6) M, had no effect on the thapsigargin and Bay K 8644 induced increase in mechanical activity. Nitrendipine, 10(-6) M, totally abolished the mechanical response in preparations stimulated by thapsigargin and Bay K 8644. In rat atrial and papillary muscles Bay K 8644 increases the frequency in right atrium and tension in both atrial and papillary muscles. Thapsigargin was without effect on the frequency and tension in the cardial preparations. In conclusion, thapsigargin increases the amplitude of spontaneous activity in rat portal veins. In contrast to Bay K 8644 thapsigargin was less effective in increasing the amplitude and had no effect on the frequency of spontaneous activity; furthermore, thapsigargin was without effect on cardiac muscles. The results support the view that an endoplasmatic Ca2(+)-pump sensitive to thapsigargin is of importance for spontaneous activity in portal veins while such pump is of minor importance for contractile activity in cardiac muscles.
Mikkelsen
E O
EO
Institute of Pharmacology, University of Aarhus, Denmark.
Poulsen
S H
SH
Christensen
S B
SB
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D011169:Portal Vein / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin
D010936:Plant Extracts; D013729:Terpenes; D019284:Thapsigargin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester