Effects of protamine sulphate on spontaneous and calcium-induced contractile activity in the rat uterus are potassium channels-mediated.
Protamine sulphate (PS) effect on spontaneous and calcium-induced rhythmic contractions of isolated virgin rat uteri was studied. PS caused dose-dependent relaxation of both types of contractions (two-way ANOVA, significant dose effects). Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME; 10(-5) mol/l), methylene blue (MB; 0.9 x 10(-6) mol/l) or propranolol (1.7 x 10(-5) mol/l) enhanced PS-mediated uterine muscle relaxation of spontaneous contractions. Dosedependent relaxation of spontaneous active isolated rat uterus with PS was lower in uteri pretreated with single dose of tetraethylammonium (TEA; 6 x 10(-3) mol/l), glibenclamide (2 x 10(-6) mol/l) and 4-aminopyridine (4-AP; 10(-3) mol/l). Calcium-induced activity of the isolated rat uterus pretreated with the same concentration of L-NAME, MB, or propranolol modified the kinetic of PS-induced relaxation without changes in EC(50) values. Pre-treatment with glibenclamide, TEA and 4-AP significantly reduce PS relaxing effect of calcium-induced activity and according to EC(50) values the order of magnitude was glibenclamide > TEA > 4-AP. PS is mixture of polyamines and may activate different signal-transduction pathways. Our results cleary demonstrate that in uterine smooth muscle PS act dominantly through potassium chanels and marginaly through beta-adrenergic receptos or nitric oxide-dependent pathways.
Orescanin-Dusić
Zorana
Z
Department of Physiology, Institute for Biological Research Sinisa Stanković, Bul. Despota Stefana 142, 11000 Belgrade, Serbia.
Milovanović
Slobodan
S
Radojicić
Ratko
R
Nikolić-Kokić
Aleksandra
A
Appiah
Isabella
I
Slavić
Marija
M
Cutura
Nedo
N
Trbojević
Stevan
S
Spasić
Mihajlo
M
Blagojević
Dusko
D
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D015221:Potassium Channels / Q000378:metabolism*; D011479:Protamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology
D015221:Potassium Channels; D011479:Protamines; D002118:Calcium