title: Beta adrenergic receptor activation attenuates the generation of inositol phosphates in the pregnant rat myometrium. Correlation with inhibition of Ca++ influx, a cAMP-independent mechanism.
abstract: In the pregnant rat myometrium, an averaged 30% of inositol phosphate accumulation induced by carbachol and oxytocin was inhibited by oxodipine indicating that a part of receptor-mediated generation of inositol phosphates depended on Ca++ influx through voltage-gated Ca++ channels. In fura-2-loaded cells, carbachol and oxytocin caused a two-phase [Ca++]i response, made up of a transient [Ca++]i peak of about 700 nM followed by a sustained phase of about 120 nM. Oxodipine reduced the [Ca++]i peak by 40% and the plateau phase by 50%, pointing to a contribution of Ca++ influx in both the [Ca++]i peak and sustained phase. Isoproterenol reduced inositol phosphate response to carbachol and oxytocin to an amount equivalent to that elicited by oxodipine. No additional reduction could be obtained in a combination of isoproterenol and oxodipine. Isoproterenol decreased by 40% the [Ca++]i peak and by 70% the [Ca++]i plateau phase. Differently from isoproterenol, forskolin did not affect inositol phosphate accumulation induced by oxytocin and failed to attenuate the [Ca++]i peak. The inhibitory effect of isoproterenol on both inositol phosphate accumulation and [Ca++]i increase induced by oxytocin was abolished by pertussis toxin. These data suggest that beta adrenergic receptor activation is linked via a cAMP-independent, pertussis toxin-sensitive process to an activation of K+ channels, as revealed by use of selective K+ channel antagonists, with the consequent closure of voltage-gated Ca++ channels, resulting in the inhibition of the Ca(++)-associated generation of inositol phosphates.
authors.affiliation: Centre National de la Recherche Scientifique URA 1131, Université Paris Sud, Orsay, France.
authors.forename: L D
authors.initials: LD
authors.lastname: Khac
authors.forename: S
authors.initials: S
authors.lastname: Arnaudeau
authors.forename: N
authors.initials: N
authors.lastname: Lepretre
authors.forename: J
authors.initials: J
authors.lastname: Mironneau
authors.forename: S
authors.initials: S
authors.lastname: Harbon
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology; D005260:Female; D007295:Inositol Phosphates / Q000096:biosynthesis*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010121:Oxytocin / Q000494:pharmacology; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D007295:Inositol Phosphates; D015221:Potassium Channels; D011943:Receptors, Adrenergic, beta; D010566:Virulence Factors, Bordetella; D010121:Oxytocin; D002217:Carbachol; D000242:Cyclic AMP; D037342:Pertussis Toxin; D010738:Type C Phospholipases; C053783:oxodipine; D007545:Isoproterenol; D000109:Acetylcholine; D002118:Calcium