TY - JOUR
T1 - Chronic oxytocin pretreatment inhibits adenylyl cyclase activity in cultured rat myometrial cells
AU - Lindeman, Karen S.
AU - Hirshman, Carol A.
AU - Kuhl, Jennifer S.
AU - Levitsky, Hyam I.
AU - Emala, Charles W.
PY - 1998/11
Y1 - 1998/11
N2 - To determine whether chronic oxytocin pretreatment inhibits adenylyl cyclase, we compared adenylyl cyclase activity in membranes prepared from cultured, immortalized rat myometrial cells that were untreated or pretreated for 24 h with oxytocin. Chronic oxytocin pretreatment (1 x 10-5 M for 24 h) attenuated basal, guanosine triphosphate (1 x 10-5 M)-, isoproterenol (1 x 10-4 M)-, forskolin (1 x 10-5 M)-, MnCl2 (20 mM)- or NaF (1 x 10-2 M)- stimulated adenylyl cyclase activity by 27 ± 5% to 39 ± 11% (n = 6, p < 0.05). Oxytocin pretreatment for 2 h (n = 5) did not produce a significant effect. To understand the mechanism by which oxytocin pretreatment decreased activity of the adenylyl cyclase pathway, we compared effects of pretreatment with either oxytocin or phenylephrine on adenylyl cyclase activity and determined the effects of G(i) inhibition and protein kinase C (PKC) depletion. Chronic (24 h) phenylephrine pretreatment (1 x 10-4 M) had effects similar to those of oxytocin pretreatment (1 x 10-5 M). PKC depletion with phorbol 12-myristate 13-acetate (1 x 10-6 M, 41 h) prevented attenuation of adenylyl cyclase activity by oxytocin pretreatment (1 x 10- 5 M for 24 h). Inhibition of G(i) by pertussis toxin pretreatment (1.25 μg/ml, 41 h) had no significant effect. These findings suggest that chronic oxytocin pretreatment desensitizes the adenylyl cyclase pathway by a cross- regulatory mechanism that involves activation of G(q) and PKC.
AB - To determine whether chronic oxytocin pretreatment inhibits adenylyl cyclase, we compared adenylyl cyclase activity in membranes prepared from cultured, immortalized rat myometrial cells that were untreated or pretreated for 24 h with oxytocin. Chronic oxytocin pretreatment (1 x 10-5 M for 24 h) attenuated basal, guanosine triphosphate (1 x 10-5 M)-, isoproterenol (1 x 10-4 M)-, forskolin (1 x 10-5 M)-, MnCl2 (20 mM)- or NaF (1 x 10-2 M)- stimulated adenylyl cyclase activity by 27 ± 5% to 39 ± 11% (n = 6, p < 0.05). Oxytocin pretreatment for 2 h (n = 5) did not produce a significant effect. To understand the mechanism by which oxytocin pretreatment decreased activity of the adenylyl cyclase pathway, we compared effects of pretreatment with either oxytocin or phenylephrine on adenylyl cyclase activity and determined the effects of G(i) inhibition and protein kinase C (PKC) depletion. Chronic (24 h) phenylephrine pretreatment (1 x 10-4 M) had effects similar to those of oxytocin pretreatment (1 x 10-5 M). PKC depletion with phorbol 12-myristate 13-acetate (1 x 10-6 M, 41 h) prevented attenuation of adenylyl cyclase activity by oxytocin pretreatment (1 x 10- 5 M for 24 h). Inhibition of G(i) by pertussis toxin pretreatment (1.25 μg/ml, 41 h) had no significant effect. These findings suggest that chronic oxytocin pretreatment desensitizes the adenylyl cyclase pathway by a cross- regulatory mechanism that involves activation of G(q) and PKC.
UR - http://www.scopus.com/inward/record.url?scp=0031769799&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031769799&partnerID=8YFLogxK
U2 - 10.1095/biolreprod59.5.1108
DO - 10.1095/biolreprod59.5.1108
M3 - Article
C2 - 9780316
AN - SCOPUS:0031769799
SN - 0006-3363
VL - 59
SP - 1108
EP - 1115
JO - Biology of reproduction
JF - Biology of reproduction
IS - 5
ER -