AlF-4 inhibits the accumulation of Ca in the endoplasmic reticulum in intact myometrial strips, but not in the rabbit ear artery.
AlF-4, known to be a potent modulator of G-proteins, also inhibits purified "P"-type cation-transport ATPases (Missiaen et al. 1988). The aim of the present work is to find out whether AlF-4 also inhibits these ATPases in intact cells. We therefore have studied the effect of AlF-4 on the force development and on 45Ca2+ -fluxes of muscle strips from rat myometrium and rabbit ear artery. 1 mM-NaF plus 10 microM-AlCl3 induces in both tissues a tonic contraction that is completely blocked by 0.5 mM-deferoxamine. The contractile response in myometrium exceeds that of the ear artery. These contractions are independent of an activation of G-proteins but their amplitude depends on [Ca2+]o. Application of AlF-4 during the loading of the endoplasmic reticulum of myometrium with Ca2+ dramatically reduces the amount of stored Ca2+ as estimated from its release induced by 1 mM-carbachol during incubation in Ca-free solution. This effect could be due to a predominant inhibitory effect of AlF-4 on the (Ca2+ + Mg2+)-ATPase of the endoplasmic reticulum. Such effect could not be established in rabbit ear artery. The increase of the fractional loss of 45Ca2+ induced by 10 microM-norepinephrine in rabbit ear artery is not inhibited by AlF-4. It is concluded that the inhibition of the endoplasmic-reticulum (Ca2+ + Mg2+)-ATPase in intact myometrial cells warns us against explaining all effects of AlF-4 on intact cells only by an activation of G-proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
Missiaen
L
L
Physiological Laboratory, Katholieke Universiteit Leuven, Belgium.
Kanmura
Y
Y
Wuytack
F
F
Raeymaekers
L
L
Declerck
I
I
Droogmans
G
G
Casteels
R
R
D000535:Aluminum / Q000494:pharmacology*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D001158:Arteries; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology; D004423:Ear / Q000098:blood supply; D004533:Egtazic Acid / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005459:Fluorides / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology / Q000648:ultrastructure*; D009215:Myometrium / Q000502:physiology / Q000648:ultrastructure*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology
D017607:Aluminum Compounds; D015220:Calcium Channels; D002712:Chlorides; D000077410:Aluminum Chloride; D004533:Egtazic Acid; D002217:Carbachol; D012969:Sodium Fluoride; D000535:Aluminum; D019204:GTP-Binding Proteins; D005459:Fluorides; D002118:Calcium; C032311:aluminum fluoride