Functional, biochemical and molecular biological evidence for a possible beta(3)-adrenoceptor in human near-term myometrium.
The possible existence of a beta(3)-adrenoceptor (beta(3)-AR) in human near-term myometrium was investigated by in vitro functional and biochemical studies and analysis of mRNA expression. SR 59119A and SR 59104A and CGP 12177 (two selective agonists and a partial agonist, respectively, of the beta(3)-AR), salbutamol and terbutaline (beta(2)-AR agonists) each produced a concentration-dependent relaxation of the myometrial spontaneous contractions. There were no differences in pD(2) values for the relaxing potencies of terbutaline, salbutamol, CGP 12177 and SR 59119A. The rank order for their relaxing efficacies was SR 59119A>SR 59104A>terbutaline approximately salbutamol approximately CGP 12177 (E(max)=52+/-7%, 42+/-12% and approximately 30% respectively). Propranolol, a beta(1)- and beta(2)-AR antagonist, and ICI 118551, a beta(2)-AR antagonist (both at 0.1 microM), did not affect the SR 59119A-induced relaxation whereas SR 59230A, a selective beta(3)-AR antagonist (1 microM), significantly reduced the maximal relaxing effect of SR 59119A. SR 59119A and salbutamol induced a significant increase in cyclic AMP levels that was antagonized by SR 59230A but not by propranolol for SR 59119A, and by propranolol but not by SR 59230A for salbutamol. The beta(3)-AR mRNA was positively expressed in myometrium preparations in a reverse transcription polymerase chain assay. The results presented provide the first evidence for the existence of the beta(3)-AR subtype in human near-term myometrium and suggest that the effects of SR 59119A might be mediated through an increase in cyclic AMP level.
Bardou
M
M
Department of Pharmacology, Faculty of Medicine Paris-Ouest, 15 rue de l'Ecole de Médecine 75006 Paris, France. Marc.Bardou@u-bourgogne.fr
Loustalot
C
C
Cortijo
J
J
Simon
B
B
Naline
E
E
Dumas
M
M
Esteve
S
S
Croci
T
T
Chalon
P
P
Frydman
R
R
Sagot
P
P
Manara
L
L
Morcillo
E J
EJ
Advenier
C
C
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000420:Albuterol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011412:Propanolamines; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; C114930:SR 59119A; D013764:Tetrahydronaphthalenes; C026777:ICI 118551; D011433:Propranolol; D000242:Cyclic AMP; D006152:Cyclic GMP; D000420:Albuterol