This study was performed to determine the action mode of oxytocin antagonist. In Study 1, the duration of in vivo action of oxytocin antagonist I (AI) was examined. After infusing AI, oxytocin was given and repeated every hour for 5 hr. Uterine activities were monitored with a polygraph. Study 2 determined the effect of AI on uterine oxytocin receptor number (Rn) and binding affinity (Kd). AI treated rats were sacrificed at 0.5 and 4 hr later for receptor assay. In Study 1, the uterine contractile response to oxytocin was significantly inhibited (p>0.05) compared to controls at five min, 1 and 2 hr after injection of AI. No differences in response were detected compared to controls (p>0.05) at later hours. In Study 2, no differences (p>0.05) between the AI and control animals in either oxytocin receptor number or binding affinity was found. These data suggest that the major mode of AI action is via competitive inhibition at the uterine oxytocin receptor and not by altering receptor number or binding affinity. AI is suggested to have the potential of being a potent and specific tocolytic agent for prevention of preterm labor in human.
Animal ; Female ; Oxytocin/pharmacology ; Oxytocin/metabolism ; Oxytocin/antagonists & inhibitors* ; Rats ; Receptors, Oxytocin/metabolism ; Uterus/physiology ; Uterus/drug effects*

This study was performed to determine the action mode of oxytocin antagonist. In Study 1, the duration of in vivo action of oxytocin antagonist I (AI) was examined. After infusing AI, oxytocin was given and repeated every hour for 5 hr. Uterine activities were monitored with a polygraph. Study 2 determined the effect of AI on uterine oxytocin receptor number (Rn) and binding affinity (Kd). AI treated rats were sacrificed at 0.5 and 4 hr later for receptor assay. In Study 1, the uterine contractile response to oxytocin was significantly inhibited (p>0.05) compared to controls at five min, 1 and 2 hr after injection of AI. No differences in response were detected compared to controls (p>0.05) at later hours. In Study 2, no differences (p>0.05) between the AI and control animals in either oxytocin receptor number or binding affinity was found. These data suggest that the major mode of AI action is via competitive inhibition at the uterine oxytocin receptor and not by altering receptor number or binding affinity. AI is suggested to have the potential of being a potent and specific tocolytic agent for prevention of preterm labor in human.
Animal ; Female ; Oxytocin/pharmacology ; Oxytocin/metabolism ; Oxytocin/antagonists & inhibitors* ; Rats ; Receptors, Oxytocin/metabolism ; Uterus/physiology ; Uterus/drug effects*

This study was designed to investigate the effect of diazepam on the spontaneous contraction and oxytocin induced contraction of the isolated rat uterus. Female rat (Sprague-Dawley) pretreated with oophorectomy and 4 days administration of estrogen. Weighing about 200 g, was sacrificed by cervical dislocation, and the uteruses were isolated. A longitudinal muscle strip was placed in temperature controlled (37℃) muscle chamber containing Locke's solution and myographied isometrically. Diazepam inhibited the spontaneous contraction and oxytocin induced contraction of the isolated rat uterus in a concentration-dependent manner. GABA, muscimol, a GABA A receptor agonist, bicuculline, a competitive GABA A receptor antagonist, picrotoxin, a non competitive GABA A receptor antagonist, baclofen, a GABA B receptor agonist, and delta-aminovaleric acid, a GABA B receptor antagonist, did not affect on the spontaneous and oxytocin induced contraction of the isolated rat uterus. The inhibitory actions of diazepam on the spontaneous and oxytocin induced contraction were not affected by all the GABA receptor agonists and antagonists, but exceptionally potentiated by bicuculline. This potentiation-effect by bicuculline was not antagonized by muscumol. In normal calcium PSS, addition of calcium restored the spontaneous contraction preinhibited by diazepam and recovered the contractile of oxtrocin preinhibited by diazepam. A23187, a calcium inophore, enhanced the restoration of both the spontaneous and oxytocin induced contraction by addition of calcium. In calcium-free PSS, diazepam suppressed the restoration of spontaneous motility by addition of calcium but allowed the recovery of spontaneous motility to a considerable extent. Diazepam could not inhibit some development of contractility by oxytocin in calcium-free PSS, but inhibited the increase in contractility by subsequent addition of calcium. These results suggest that the inhibitory action of diazepam on the rat uterine motility does not depend on or related to GABA receptors and that diazepam inhibits the extracellular calcium influx to suppress the spontaneous and oxytocin induced contractilities.
Animals ; Baclofen ; Bicuculline ; Calcimycin ; Calcium ; Diazepam* ; Dislocations ; Estrogens ; Female ; GABA Agonists ; GABA-A Receptor Agonists ; GABA-A Receptor Antagonists ; GABA-B Receptor Agonists ; GABA-B Receptor Antagonists ; gamma-Aminobutyric Acid ; Humans ; Muscimol ; Ovariectomy ; Oxytocin* ; Picrotoxin ; Rats* ; Receptors, GABA ; Uterus*

To establish a new amino acid structure descriptor that can be applied to polypeptide quantitative structure activity relationship (QSAR) studies, a new descriptor, SVRDF, was derived from a principal components analysis of a matrix of 150 radial distribution function index of amino acids. The scale was then applied in three panels of peptide QSAR that were molded by partial least squares regression. The obtained models with the correlation coefficients (R2(cum)), cross-validation correlation coefficients (Q2(cum)) were 0.766 and 0.724 for 48 bitter tasting dipeptides; 0.941 and 0.811 for 21 oxytocin analogues; 0.996 and 0.919 for 20 thromboplastin inhibitors. Satisfactory results showed that information related to biological activity can be systemically expressed by SVRDF scales, which may be an useful structural expression methodology for the study of peptides QSAR.
Amino Acid Sequence ; Amino Acids ; chemistry ; Dipeptides ; chemistry ; pharmacology ; Least-Squares Analysis ; Models, Chemical ; Oxytocin ; analogs & derivatives ; chemistry ; pharmacology ; Peptides ; chemistry ; pharmacology ; Principal Component Analysis ; methods ; Quantitative Structure-Activity Relationship ; Thromboplastin ; antagonists & inhibitors ; chemistry ; pharmacology

OBJECTIVETo observe effects of Fufang Xiaojingtong capsules (FXJTC) on activities of the uterine smooth muscle of the rat in vitro and the uterus of the rabbit in vivo.

METHODThe isolated rat uterine smooth muscle strips were mounted in a Magnus bath containing Locke's solution with a final content of 12.48, 6.24 or 3.12 mg x mL(-1) of FXJTC at 37 degrees C; and 2.0, 1.0 and 0.5 g x kg(-1) of FXJTC and 2.0 g x kg(-1) of Tianqi Tongjing capsules were respectively given to the rabbits through the duodenum, respectively. Their effects on frequency, amplitude and activity of contraction of the rat uterus in vitro and the rabbit uterus in vivo were investigated.

RESULTFXJTC could significantly inhibit the frequency, amplitude and activity of contraction of the normal rat uterus in vitro and decrease the oxytocin-induced increase of contraction of the rabbit uterus in vitro; lowered the frequency, amplitude and activity of contraction of the rabbit uterus in vivo and inhibit the oxytocin-induced the strengthening of contraction of the rabbit uterus in vivo.

CONCLUSIONFufang Xiaojingtong capsules maybe used for treatment of dysmenorrhea induced by spasm of uterine smooth muscle.

Animals ; Capsules ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Female ; In Vitro Techniques ; Muscle Contraction ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; Oxytocin ; antagonists & inhibitors ; Plants, Medicinal ; chemistry ; Rabbits ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Uterus ; drug effects ; physiology