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*

One of the core symptoms in anxiety disorders is dysregulated fear response. It is crucial for psychologists and neuroscientists to understand how fear responses are enhanced and inhibited. Although oxytocin (OXT) was initially conceived as a prosocial molecule and mammalian neuropeptide that enhances cooperation and trust, later studies showed that it produces modulatory influence on fear responses. Therefore, OXT is now regarded as a promising pharmacological agent to boost treatment response in anxiety disorders. However, the effect of OXT on fear responses have been somewhat complex, and there are some contradictions among animal experiments and human studies. In this article, we summarize recent studies that employed animal models, brain region-specific manipulations and preclinical studies to explore the role of OXT in the acquisition and processing of fear response. We also discuss the methodological differences among these studies and review the potential factors that may contribute to the complicated effect of OXT on fear response. This review will help to promote the potential clinical application of OXT.
Animals ; Brain ; drug effects ; Fear ; drug effects ; Humans ; Oxytocics ; pharmacology ; Oxytocin ; pharmacology

OBJECTIVE: To investigate the effect of Heliotropium indicum L. (H. indicum L.) on uterine involution and its underlying mechanisms in both in vivo and in vitro study. METHODS: For in vivo studies, postpartum rats were randomly divided into 2 groups (n=24 for each): control group and treated group which were orally and daily administered with ethanolic extract of H. indicum L. (250 mg/kg body weight) until day 5 of postpartum. Uteri were collected for analysis of weight, cross-sectional area, collagen cross-sectional area, and collagen content on postpartum day 1, 3, and 5 (n=8 for each) from both groups. Blood samples were collected for hepatotoxicity and 17β-estradiol (E₂) measurement. For in vitro studies, the extract effects on uterine contraction at half maximum effective concentration of 2.50 mg/mL were studied in organ bath system for at least 20 min. RESULTS: Uterine parameters were significantly decreased after treated with extract of H. indicum L. (P<0.05). H. indicum L. extract significantly accelerated the reduction of those parameters and significantly decreased E₂ (P<0.05). The extract facilitated uterine involution with no hepatotoxicity. H. indicum L. extract significantly stimulated uterine contraction (P<0.05) and synergized with oxytocin, prostaglandin and its precursor, linoleic acid. By investigating the different sequencing of the extract with the additional stimulants (added before or after), the two showed antagonistic effects, but still showed potentiated force when compared with control (without the stimulants). CONCLUSIONS The underlying mechanisms by which H. indicum L. facilitated uterine involution might be due to reducing E₂ which induces collagenase activity, leading to decreases in uterine weight and size and stimulating uterine contraction. Our study provides new findings for future drug development for facilitating uterine involution with H. indicum L.
Pregnancy ; Female ; Rats ; Animals ; Heliotropium ; Uterus ; Plant Extracts/pharmacology* ; Oxytocin ; Collagen/pharmacology*

Morphine is known to inhibit nocturnal uterine contractions in several animal models, and oxytocin is known to be a primary causative factor of uterine contractions. The purpose of the present study was to determine the tocolytic effect of morphine in relation to the pharmacokinetics of oxytocin, after a bolus injection of oxytocin. The metabolism of oxytocin was investigated during the third trimester in baboons. Four animals were placed on a tether system with venous and arterial access, including continuous uterine monitoring. Plasma oxytocin levels were determined by radioimmunoassay after extraction with petroleum ether/acetone. Morphine consistently increased the metabolic clearance rate of oxytocin in all four animals (p < 0.05) and this was in accordance with suppressed uterine contractions. We conclude that morphine could be used as an inhibitor of nocturnal uterine contractions, and that this is caused by the morphine induced increased metabolic clearance rate of oxytocin.
Animal ; Female ; Metabolic Clearance Rate ; Morphine/*pharmacology ; Oxytocin/*pharmacokinetics ; Papio ; Pregnancy ; Tocolytic Agents/*pharmacology ; Uterine Contraction/drug effects

OBJECTIVETo observe the effect of electroacupuncture (EA) of different acupoints on abnormal electrohysterogram (EHG) in pregnant rats, so as to analyze their regularities in regulating dysfunction of the viscera.

METHODSA total of 48 Wistar pregnant rats (18-20 days) anesthetized with mixture solution of 1.5% chloralose and 25% urethane (i. p) were randomized into control (n=10), "Sanyinjiao" (SP 6, n=9), "Hegu" (LI 4, n=8), "Neiguan" (PC 6, n=0), and "SP 6 + LI 4" (n=11) groups. EHG was recorded by using a bipolar stainless steel electrode inserted in the sub-perimetrium layer of the left mid part of the uterus. The reference electrode was placed beneath the skin of the incision. Oxytocin and gesterol were given to the local uterus nearby the recording electrode to induce abnormal excitement and suppression of EHG respectively. EA (1-2 mA, 2/15 Hz) was applied to the above-mentioned acupoints separately for 20 min in the EA groups and the influences of EA on the amplitude and frequency of burst (fast) waves and slow waves of EHG were analyzed.

RESULTSCompared with the control group, EA of SP 6 + LI 4 and SP 6 groups had apparent inhibitory effects on oxytocin-induced increases of the frequency and amplitude of both fast and slow waves (P<0.05); and EA of LI 4 also had a markedly inhibitory effect on the amplitude of fast waves (P<0.05). No marked effects on both frequency and amplitude of fast waves and slow waves of EHG were found in the PC 6 group (P>0.05). In comparison with the control group, EA of SP 6+LI 4 and SP 6 could relieve or significantly relieve progesterone-induced suppression of the frequency and amplitude of both fast and slow waves (P<0.05); and the effects of SP 6 + LI 4 appeared earlier and lasted longer than those of SP 6; while EA of LI 4 and PC 6 had no obvious effect on progesterone-induced changes of the frequency and amplitude of both fast and slow waves (P>0.05).

CONCLUSIONEA different acupoints have their own relative specificity in regulating abnormal EHG.

Acupuncture Points ; Animals ; Electroacupuncture ; Female ; Myometrium ; physiology ; Oxytocin ; pharmacology ; Pregnancy ; Pregnancy, Animal ; physiology ; Progesterone ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar

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

The objective of this study was to investigate the effects of oxytocin infusion on corpus luteum (CL) function during early to mid-diestrus by measuring luteal size (LS) and luteal blood flow (LBF) along with plasma levels of progesterone (P4) and prostaglandin metabolites (13,14-dihydro-15-keto-prostaglandin F2alpha, PGFM). On day (D) 7 of the estrus cycle (D1 = ovulation), seven cows received 100 IU of oxytocin (OXY) or placebo (PL) following a Latin square design. LS and LBF increased in both groups over time and no differences were observed between the groups. PGFM did not differ either within the groups over time or between the groups at any time point. P4 of the OXY group was higher compared to that of the the PL group 360 min after the infusion (p = 0.01) and tended to be higher at the time points 450 min, 48 h, and 72 h (all p = 0.08). Results from this study support the hypothesis that OXY is not directly involved in the mechanism(s) governing blood flow of the CL and has no remarkable effects either on luteal size or P4 and PGFM plasma levels. Further investigation is needed to elucidate the role of OXY in CL blood flow during early and late luteal phases.
Animals ; Cattle/*physiology ; Corpus Luteum/blood supply/*drug effects/secretion/ultrasonography ; Dinoprost/analogs & derivatives/blood ; Estrous Cycle/*drug effects/physiology ; Female ; Immunoenzyme Techniques/veterinary ; Organ Size/physiology ; Oxytocin/*pharmacology ; Progesterone/blood/*secretion ; Random Allocation ; Ultrasonography, Doppler, Color/veterinary

OBJECTIVETo observe effects of Shujing Ketong soft capsules (SJKTSC) on activities of the uterine of the rat in vitro and in vivo.

METHODThe isolated rat uterine were mounted in the improved Genell solution with a final content of 0. 96, 1.92, 3.84 microg x g(-1) of SJKTSC at 37 degrees C; and 9. 6, 19. 2, 38.4 mg x kg(-1) of SJKTSC and 2 g x kg(-1) of Tongjingbao granules were given to the rat through the duodenum respectively. Their effects on frequency, amplitude and activity of contraction of rat uterus in vitro and in vivo were investigated.

RESULTSJKTSC 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 rat uterus in vitro; lowered the frequency, amplitude and activity of the oxytocin-induced contraction of the rat uterus in vivo and inhibit the oxytocin-induced the strengthening of contraction of the rat uterus in vivo.

CONCLUSIONShujing Ketong soft capsules maybe used for treatment of dysmenorrhea induced by spasm of uterine smooth muscle.

Animals ; Capsules ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Dysmenorrhea ; drug therapy ; physiopathology ; Female ; In Vitro Techniques ; Muscle, Smooth ; drug effects ; physiology ; Oxytocin ; adverse effects ; Rats ; Rats, Wistar ; Time Factors ; Uterine Contraction ; drug effects ; Uterus ; drug effects ; physiology

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