Activity Of Uterine Smooth Muscle Research Articles

Multichannel mapping of in vivo rat uterine myometrium exhibits both high and low frequency electrical activity in non-pregnancy

The uterus exhibits intermittent electrophysiological activity in vivo. Although most active during labor, the non-pregnant uterus can exhibit activity of comparable magnitude to the early stages of labor. In this study, two types of flexible electrodes were utilized to measure the electrical activity of uterine smooth muscle in vivo in anesthetized, non-pregnant rats. Flexible printed circuit electrodes were placed on the serosal surface of the uterine horn of six anesthetized rats. Electrical activity was recorded for a duration of 20–30 min. Activity contained two components: high frequency activity (bursts) and an underlying low frequency ‘slow wave’ which occurred concurrently. These components had dominant frequencies of 6.82 ± 0.63 Hz for the burst frequency and 0.032 ± 0.0055 Hz for the slow wave frequency. There was a mean burst occurrence rate of 0.76 ± 0.23 bursts per minute and mean burst duration of 20.1 ± 6.5 s. The use of multiple high-resolution electrodes enabled 2D mapping of the initiation and propagation of activity along the uterine horn. This in vivo approach has the potential to provide the organ level detail to help interpret non-invasive body surface recordings.

Effect of processing with vinegar on efficacy of Curcuma longa in treatment of dysmenorrhea in rats with syndrome of liver depression and Qi stagnation

This study compared the effects of Curcuma longa before and after processing with vinegar on the rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation to reveal the mechanism of vinegar processing in improving the role of C. longa in soothing liver and relieving pain. The rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation was established according to the Preparation of the Animal Model of Dysmenorrhea(Draft) and the chronic unpredictable stress me-thod. The changes in the body weight, organ indexes, writhing latency, writhing score, and serum levels of six liver function indicators, sex hormones, pain factors, and blood rheological indicators were measured to evaluate the efficacy of C. longa processed with vinegar or not in treating dysmenorrhea in the rats with syndrome of liver depression and qi stagnation. Compared with the model group, the C. longa group(processed with vinegar or not) showed slow weight loss, increase in writhing latency, and decrease in writhing response(P<0.05). The inhibition rates on writhing in raw C. longa, vinegar-processed C. longa, and positive groups were 33.780%, 64.611%, and 62.466%, respectively. The significantly higher inhibition rate of the vinegar processing group indicated that vinegar-processed C. longa demonstrated more significant therapeutic effect. The vinegar-processed C. longa group showed lower levels of alanine aminotransferase(ALT), alkaline phosphatase(ALP), aspartate aminotransferase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) and higher level of albumin(ALB)(P<0.05), which indicated that vinegar processing enhanced the therapeutic effect of C. longa on liver injury. The serum levels of estradiol(E_2) and oxytocin(OT) were lower in the vinegar-processed C. longa group(P<0.05), indicating that the vinegar-processed C. longa could regulate the sex hormone levels, reduce the activity of uterine smooth muscle and contraction of uterus, and alleviate the symptoms of dysmenorrhea in rats. Moreover, the vinegar-processed C. longa group showed lower interleukin-6(IL-6) and arginine vasopressin(AVP) levels and higher beta-endorphin(β-EP) level(P<0.05), which indicated that vinegar-processed C. longa regulated the levels of pain factors to exert the pain-relieving effect. Drug intervention decreased the whole blood viscosity low-cut, medium-cut and high-cut values, plasma viscosity, whole blood reduction viscosity low-cut and high-cut values, erythrocyte cumulative pressure, and equation K value of erythrocyte sedimentation rate(P<0.05), and the vinegar-processed C. longa group outperformed other groups. This result indicated that vinegar processing enhanced the function of C. longa in improving the local blood rheology. C. longa processed with vinegar can enter the liver to relieve the da-mage to the heart, liver, kidney, and uterus, repair the liver function, and recover the sex hormone levels and immune function by regulating the levels of sex hormones and pain factors and improving the blood rheology. It activates the pain-relieving mechanism to relieve the pain, protect the liver, and fight inflammation, which is consistent with the theory that vinegar processing facilitates C. longa entering the liver to sooth liver and relieve pain.

EFFECTS OF SESAMUM RADIATUM AQUEOUS LEAF EXTRACT ON RHYTHMIC CONTRACTIONS OF UTERINE SMOOTH MUSCLE BUNDLES FROM PREGNANT RATS

Sesamum radiatum is employed in traditional medicine for parturient women to facilitate deliveries. In this study, the effects of the aqueous leaf extract were examined on the contractile activity of uterine smooth muscle isolated from pregnant Wistar rats (19-21 days). The isometric contractile force of the uterine smooth muscle bundles was recorded by using a strain gauge. S. radiatum aqueous leaf extracts (ESera, 1×10 -4 µg/ml - 100µg/ml) showed uterotonic properties. These uterotonic effects were characterized by the increase of the amplitude, the frequency and the basal tone of the uterine smooth muscle strips in normal Mac Ewen solution and by the development of contracture in depolarizing solution and in solution without calcium. Similar effects were observed with Oxytocin (OT, 2.5×10 -14 µg/ml - 2.5×10 -9 µg/ml) and misoprostol (Miso, 1×10 -3 µg/ml - 0.08µg/ml). In Ca 2+ -free solution, the addition of the ESera (10 µg / ml) elicited the development of contracture in the presence of EGTA (0.1 mM). This result suggests that ESera could act on the double calcium flux (intracellular and extracellular) like misoprostol, a synthetic analogue of prostaglandin E1. In conclusion, the aqueous leaf extract of S. radiatum (ESera) had uterotonic effects (prostaglandin-like activity) on uterine contraction in pregnant rats.

Effects of sulphonylureas on spontaneous motility and induced contractions in rat isolated uterus.

To clarify the action of sulphonylureas on calcium, the effect of tolbutamide and glibenclamide has been investigated on a Ca-dependent process, the contractile activity of uterine smooth muscle. Both sulphonylureas antagonized the contractions evoked by CaCl2 in a non-competitive manner when the uterus was maintained in depolarizing solution and did not affect the spontaneous contractions of rat uterus. The capacity of tolbutamide and glibenclamide to relax vanadate-induced contraction of rat uterus in Ca-free medium suggests that sulphonylureas may have an intracellular site of action related to cytosolic free Ca levels, or effect a reduction in Ca action.

In Situ Calcium Signaling

Controlled uterine smooth muscle activity is essential for our reproductive health. While we understand reasonably well the steps that produce contraction following a rise in intracellular [Ca], the mechanism controlling excitability and thus the rise of Ca, is less well understood. Here we examine the role of the internal Ca sore, the sarcoplasmic reticulum (SR), and its relation to surface membrane ion channels. We show that despite having a well-developed SR, the rat uterus does not produce the elemental and local Ca signals, known as Ca sparks. This in turn has consequences for excitability, as the negative feedback loop between these Ca signals and Ca-activated K (BK) channels on the surface membrane is lost. This may be important for producing the powerful long-lasting contractions of the uterus required during labor.

Effects of tachykinins on uterine smooth muscle.

1. Sensory nerves supplying the mammalian uterus have been shown to contain substance P (SP) and neurokinin (NK)A. This review presents some of the advances that have led to a greater understanding of the effects of tachykinins on uterine smooth muscle. 2. The cell-surface peptidase neprilysin (EC.3 24.11, endopeptidase 24.11, enkephalinase, CALLA, CD10) has been shown to play a major role in regulating the actions of tachykinins on both rat and human myometrium. Because this peptidase is known to be regulated by steroids and pregnancy, its effects may be of physiological relevance. 3. Tachykinins produce contractions of isolated myometrial preparations from non-pregnant rats and mice. The NK2 receptor mediates these effects in rat uterus, while the NK1 receptor may mediate these effects in the mouse uterus. 4. The effects of tachykinins have been examined on myometrial preparations obtained at Caesarean section from near-term pregnant women. In the presence of the peptidase inhibitors (thiorphan, captopril and bestatin), the mammalian tachykinins SP, NKA and NKB produced concentration-dependent uterine contractions. 5. The order of agonist potency NKA > SP = NKB suggested that NK2 receptors mediate uterine contractions in the human. This was confirmed using the stable analogues [Sar9,Met(O2)11]SP, [Lys5MeLeu9Nle10]NKA(4-10) and [N-MePhe7]NKB, which are NK1, NK2 and NK3 receptor selective, respectively. Only [Lys5MeLeu9Nle10]NKA(4-10) produced concentration-related contractions of human uterine smooth muscle. 6. The experimental findings described in the present review, taken together with results published previously in the literature, indicate that tachykinin peptides may play a physiological or pathophysiological role in regulating uterine smooth muscle activity. However, more extensive research will be required to confirm such a role for these peptides.

Effect of xanthorrhizol, xanthorrhizol glycoside and trachylobanoic acid isolated from Cachani complex plants upon the contractile activity of uterine smooth muscle.

Xanthorrhizol, xanthorrhizol glycoside, and trachylobanoic acid, compounds isolated from medicinal plants that are grouped in the complex known as Cachani have been shown to inhibit the tonic contraction of rat uterus induced by: (a) depolarizing K+ solution (60 mM), (b) CaCl2 (1 mM), and (c) BAY K 8644 (0.3 microM) in a concentration-dependent manner (1-30 micrograms/mL). The inhibitory potency was displayed as follows: xanthorrhizol > xanthorrhizol glycoside > trachylobanoic acid. These results suggest that the assayed compounds might block voltage operated calcium influx in myometrial cells as they displayed a calcium-antagonistic activity. This effect is not due to peripheral receptor activation (beta 2-adrenergic, H2-histaminergic) as neither propranolol nor cimetidine modified the inhibitory effect of the compounds assayed. This is the first report showing that plants belonging to the Cachani complex may contain uterine smooth muscle bioactive substances.

Effects of leaf extract of Caesalpinia bonduc (Caesalpiniaceae) on the contractile activity of uterine smooth muscle of pregnant rats

The calcium dependency and the cholinergic effect of the leaf extract of Caesalpinia bonduc Roxb. (Caesalpiniaceae) was studied in isolated pregnant rat myometrium preparations. Isometric contractions were recorded. The extract (Cebo) increased the contractile force in the isolated strips in a concentration-dependent manner. The effects were comparable to those obtained with acetylcholine. Contractions induced by Cebo or acetylcholine were inhibited in the presence of atropine. The stimulating action of Cebo on the contractile responses of isolated myometrium preparations inhibited by atropine may be mediated by cholinergic receptors. In calcium-free solution Cebo induced a tonic contraction (contracture) of the muscle. Moreover, in high-potassium calcium-free solution Cebo caused contracture of the uterine smooth muscle. Cebo was still able to elicit contractions in calcium-free solution containing EDTA or EGTA. These findings suggest the existence of cholinergic receptors sensitive to Cebo which could influence the influx of calcium (phasic contraction) and mobilization of calcium from cellular stores (tonic contraction), both of which are responsible for the increase of contractile activity and development of the contracture of uterine smooth muscle.

Actions of Placental and Fetal Adrenal Steroid Hormones in Primate Pregnancy*

It is clear that steroid hormones of placental and fetal adrenal origin have critically important roles in regulating key physiological events essential to the maintenance of pregnancy and development of the fetus for extrauterine life. Thus, progesterone has suppressive actions on lymphocyte proliferation and activity and on the immune system to prevent rejection of the developing fetus and placenta (see Fig. 9). Progesterone also suppresses the calcium-calmodulin-MLCK system and thus activity of uterine smooth muscle, thereby promoting myometrial quiescence to ensure the maintenance of pregnancy. Estrogen enhances uteroplacental blood flow and possibly placental neovascularization to provide optimal gas exchange and the nutrients required for the rapidly developing fetus and placenta. In turn, estrogen has specific stimulatory effects on the receptor-mediated uptake of LDL by, and P-450scc activity within, syncytiotrophoblasts, thus promoting the biosynthesis of progesterone. Moreover, there is an estrogen-dependent developmental regulation of expression of the LDL receptor and NAD-dependent 11 beta-HSD in the placenta, processes reflecting functional/biochemical differentiation of the trophoblast cells with advancing gestation. The increase in 11 beta-HSD causes a change in transplacental corticosteroid metabolism, which results in activation of the HPAA in the fetus. As a result of this cascade of events, there is an increase in expression of pituitary POMC/ACTH and key enzymes, e.g. 3 beta-HSD and P-450 17 alpha-hydroxylase, important for de novo cortisol formation by, and consequently maturation of, the fetal adrenal gland. In turn, cortisol has well defined actions on surfactant biosynthesis and consequently fetal lung maturation, as well as effects on placental CRH/POMC release, which may be important to the initiation of labor. At midgestation, estrogen also selectively feeds back on the fetal adrenal to suppress DHA and maintain physiologically normal levels of estrogen. Preparation of the breast for lactation and nourishment of the newborn appears to involve a multifactorial system of regulation that includes estrogen. It is apparent, therefore, that autocrine/paracrine, as well as endocrine, systems of regulation are operative within the fetoplacental unit during primate pregnancy. A major goal of this review has been to illustrate the critically close functional communication existing between the developing placenta and fetus in the biosynthesis and the actions of steroid hormones during primate pregnancy. The functional interaction of the human fetal adrenal and placenta with respect to the biosynthesis of estrogen was demonstrated many years ago. However, the recent studies presented in this review show that the endocrine interaction between the fetus and placenta is more extensive, involving complex physiological regulatory mechanisms. Thus, as illustrated in Fig. 9, estrogen, acting via its receptor within the placenta and other reproductive tissues, orchestrates the dynamic interchange between the placenta and fetus responsible for the developmental regulation of the biosynthesis of the various steroid and peptide hormones and their receptors necessary for the maintenance of pregnancy and development of a live newborn. It would appear, therefore, that the immediate and long range challenges in this area of reproductive endocrinology are to employ in vitro molecular and in vivo experimental approaches simultaneously to elucidate the nature of these complex interactions and define the cellular and molecular mechanisms underlying these important regulatory events.

Vascularization of human endometrium. Uterine blood flow in healthy condition and in primary dysmenorrhoea.

The anatomy of the human uterine vascular tree changes repeatedly with the variations in hormonal state during each menstrual cycle, with progressive differentiation of arterioles up to the premenstrual state. Hormonal factors also influence the innervation of uterine arteries, both cholinergic, adrenergic and peptidergic, and regulate the spontaneous contractile activity of the smooth muscle of vessel walls as well as the motor responses of these tissues to different vasoactive substances. The smaller branches of uterine arteries, i.e., the resistance arteries appear to be of particular importance in the regulation of uterine blood flow, since they are most densely innervated. Furthermore, the most effective uterine vasoconstrictors in vitro, vasopressin, endothelin, oxytocin and noradrenaline have a more pronounced effect on these vessels than on the main branches of the uterine artery. Vascular compression may also result from changes in the myometrial activity. A hormonal disturbance may cause dysfunctional bleeding by changing vessel growth as well as the uterine smooth muscle activity of both vessels and myometrium. An example of the latter phenomenon is primary dysmenorrhoea, women with this condition having an increased secretion of vasopressin. By an action on type V1 vasopressin receptors of the uterus, this peptide causes myometrial hyperactivity and vasoconstriction, with resultant uterine ischemia and pain. Further support for a pathophysiological role of vasopressin and also of oxytocin in dysmenorrhoea is the therapeutic effect of a competitive type V1 vasopressin and oxytocin receptor antagonist in the condition.

Relaxin increases rat heart rate by a direct action on the cardiac atrium

Relaxin (Rlx) is best understood as a protein hormone of pregnancy that can influence pelvic and cervical connective tissue as well as uterine smooth muscle activity. Thus, it was unexpected that dense Rlx binding sites would be found in the rat cardiac atrium. To functionally characterize this finding, isolated rat atria were challenged with Rlx (0.3 to 30 ng/ml), and they responded with an increased rate (+36%) and force (+38%) of contraction Further studies in conscious normotensive and spontaneously hypertensive rats established by minipump circulating Rlx levels of about 0.5 and 5 ng/ml over 1 to 2 wks. There were significant increases in heart rate of 10–15%, with no consistent changes in blood or urine volume, water or food intake, and mean arterial pressure. We conclude that Rlx can directly stimulate rat cardiac atrial activity in vitro and cause chronotropy in vivo.

Propagation of electrical and mechanical activity in uterine smooth muscle: A functional role for stretch-sensitive channels

Propagation of electrical and mechanical activity in uterine smooth muscle: A functional role for stretch-sensitive channels

Endothelin in perinatal pharmacology.

E ndothelin (ET) is a potent vasoconstrictor peptide that was initially isolated from the conditioned medium of the cultured porcine aortic endothelial cells.’ It contains 21 amino acidresidues including two intramolecular disulfide linkages. Subsequently, analysis of the human endothelin gene showed existence of three human endothelin genes, predicting the three distinct isotypes of ET designated ET-l, ET-2 and ET-3 (Fig l).’ Interestingly, an amino acid sequence very similar to ET was found in the sequence of a snake venom sarafotoxin S6b.3 Human, porcine, dog, and rat ET-1s have the identical amino acid sequences. It is now well-known that the cluster of the hydrophobic amino acid residues at the carboxy1 terminus of the peptide, particularly the terminal Trp21, aminoterminus carboxyl groups of Asp8 and GlulO and the aromatic group of Phel4 are very important in exerting the potent vasoconstriction.4,5 Further investigations have demonstrated widespread binding sites for ET-1 not only in vascular bed but also in lung, adrenal gland, nervous systems, and other organs.6 In addition, widespread transcription of ET-l mRNA was found in various tissues including neurons,7,8 suggesting a variety of physiological roles of ET. ET causes a slow-developing and long-lasting vasoconstriction in almost all arteries and veins.’ The concentration to induce vasoconstriction is very low, although ET exhibits different potencies depending on the vessel and species employed.1,g ET binds to a specific receptor on smooth muscle membrane and activates phospholipase C, producing phosphoinositol 1, 4, 5,-trisphosphate. The latter elicits the release of calcium ion from the caffeine-sensitive calcium store, inducing constriction. On the other hand, ET stimulates calcium channels of the smooth muscle membrane, inducing influx of exterior calcium ion in porcine coronary artery.“’ The activated influx of calcium ion prolongs the duration of intracellular calcium signal. However, several reports suggested no responsibility of extracellular calcium influx for endothelininduced vasoconstriction. There is still a controversy on this problem. ET elicits a constriction not only in vascular smooth muscle but also in nonvascular smooth muscle.g ET causes rhythmic contractions in nonpregnant human and rat uterine muscles. The contractile frequency increases. Concomitantly sustained tonic contraction appears. In the presence of dihydropyridine calcium antagonist, the increase in frequency of rhythmic contraction induced by ET is completely abolished whereas the sustained increase in tonic contraction is insensitive to external calcium ion.i1,12 This phenomenon is very similar to the oxytotin-induced contraction. Oxytocin stimulates both frequency and force of contractile activity in uterine smooth muscle. Oxytocin initiates spike discharges and increases the frequency. ET also elicits an increase in the number of spikes in a similar manner in rat portal vein.i3 However, WC have no information on uterine muscle. In case of oxytocin, these effects are highly dependent on the stage of gestation. We have no further information on the hormonal effect on the ET-induced contraction of uterine smooth muscle. In this connection, it is interesting that ET was detected in supra-optic and paraventricular nuclei and posterior lobe of pituitary.‘* Distribution of ET in this region is very similar to vasopressin. In addition, water deprivation depleted completely ET from the posterior lobe of pituitary, suggesting the role of ET in water balance.14 Oxytocin is also synthesized in the same region. However, neurons containing oxytocin are distinct from those of vasopressin. Recently Stojilbovic et ali5 demonstrated that ET releases luteinizing hormone (LH) and follicle-

Characterization of the spontaneous motor activity of the isolated human pregnant myometrium

The motor activity of myometrial strips from pregnant human uterus was characterized in vitro by the use of inhibitory compounds acting on the smooth muscle contractility at different levels. Spontaneous contractions were not inhibited by tetrodotoxin or a series of membrane receptor antagonists, like anticholinergics, antihistaminics, α-adrenergic blocking agents, antiserotoninergics and opioid receptor antagonists, thus excluding neuronal involvements or a local release of endogenous mediators active on the respective membrane receptors. The ineffectiveness of indomethacin (10 −5 m) minimizes a role for excitatory prostaglandins. Isoprenaline and selective β 2-adrenergic stimulants, like salbutamol and hexoprenaline (up to 10 −5 m), failed to affect the amplitude of spontaneous contractions. Conversely the adenylate cyclase activator, forskohn, had a concentration-dependent inhibitory effect. Ca 2+-free medium, trifluoperazine and all the calcium channel blockers examined produced a concentration-dependent inhibition of the spontaneous contractions in the following order of sensitivity: nifedipine ≫ verapamil ≫ diltiazem > trifluoperazine.The inhibitory effect of nifedipine was not overcome by excess calcium concentration in the bathing medium, but was completely restored by addition of the calcium agonist Bay K 864410 −7 m. From these data it can be concluded that the spontaneous activity of pregnant human myometrium in vitro is independent of neural or humoral mechanisms. The inhibitory effect of Ca 2+-free medium and the efficacy of calcium channel blockers support the view that calcium influx is an important step in initiating the contractile activity of uterine smooth muscle.

The zoapatle XV. Activity of 16a-hydroxy-ent-kauran-19-oic acid isolated from montanoa hibiscifolia, and its methyl ester on rat and guinea pig uterus

16α-Hydroxy-ent-kauran-19-oic acid was isolated from Montanoa hibiscifolia. The effects of this acid and its methyl ester on the contractile activity of rat and guinea pig uterine horns were studied. Both inhibited spontaneous, oxytocin-induced and potassium-induced contractile activities. The inhibitory effect produced by the methyl ester was greater than that observed with the acid. The methyl ester was 2–5 times more potent than the acid upon spontaneous and potassium-induced contractions and 11–15 times more potent than the acid upon the contractile activity of uterine smooth muscle induced by oxytocin. Such effects were observed using bath concentrations of 6, 15, 30 and 60 μM of each compound.

The effect of galanin, CGRP and ANP on spontaneous smooth muscle activity of rat uterus

In the present study the effect of the newly isolated peptides galanin, calcitonin gene-related peptide (CGRP) and atrial natriuretic peptide (ANP) was examined on spontaneous uterine smooth muscle activity on the rat in vitro. Galanin showed a slight and insignificant stimulatory effect on the amplitude, while both CGRP and ANP were found to be potent inhibitors of the uterine smooth muscle contractions. In connection with the recent demonstration of galanin and CGRP nerves in the genital tract, these pharmacological findings suggest that the peptides may participate in the control of nervous control of uterine muscular activity, although the exact physiological roles remain to be clarified.

Vasoactive intestinal polypeptide (VIP) increases vaginal blood flow and inhibits uterine smooth muscle activity in women.

The human vagina and uterus are heavily innervated by VIP-containing nerve fibres. In the present study, we have measured vaginal blood flow, transmucosal oxygen tension and uterine smooth muscle activity during stepwise intravenous infusion of vasoactive intestinal polypeptide (VIP) (0, 100, 300, 900 pmol kg-1 h-1) in non-pregnant women. Vaginal blood flow was measured by the heat clearance technique, transmucosal oxygen tension by an O2-electrode and uterine activity by a micro-tip pressure catheter in the uterine cavity. Arterial blood pressure, pulse frequency and the concentration of VIP in peripheral venous blood were monitored. VIP induced a concentration-dependent increase in vaginal blood flow. The transmucosal oxygen tension was not significantly changed by VIP. The maximum dose of VIP decreased systolic as well as diastolic blood pressure and increased pulse frequency. VIP inhibited uterine activity. These findings suggest that VIP participates as a neurotransmitter in the control of genital physiological responses.

Vasoactive intestinal polypeptide (VIP): Effect on rabbit uterine smooth muscle in vivo and in vitro

The effect of vasoactive intestinal polypeptide (VIP) on uterine smooth muscle electrical and mechanical activity in non-pregnant estradiol-treated rabbits was investigated using in vivo and in vitro methods. The studies were performed on spontaneous, oxytocin-, carbachol-, and prostaglandin-42 alpha-induced activity. VIP had a dose-related inhibitory effect on both myoelectrical and mechanical activity. The concentration needed for 50% inhibition (ID50) was 2 x 10(-10) mol VIP . 1(-1) (in vivo), an 6 x 10(-8) mol VIP . 1(-1) (in vitro). This inhibition was unaffected by the presence of atropine (10(-5) mol . 1(-1)), propranolol (10(-5)), phentolamine (10(-5)), naloxone (10(-5)), apamin (10(-5)), and tetrodotoxin (10(-5)). These findings indicate that VIP may act via a specific receptor on the smooth muscle and supports the hypothesis that VIP may be a neurotransmitter involved in the local nervous control of uterine smooth muscle activity.

Vasoactive intestinal polypeptide (VIP) in the human female reproductive tract: distribution and motor effects.

The distribution and concentration of vasoactive intestinal polypeptide (VIP) in the human female genital tract were studied by means of immunohistochemistry and immunochemistry. Further, the effect of VIP (10�#{176}-10’M) on the mechanical activity of uterine smooth muscle was investigated. Generally, VIP immunoreactive nerve fibers were distributed among smooth muscle cells and around vessels. They were most abundant in the isthmic part of the Fallopian tube, the Outer and inner Ostium of the cervix, and in the vagina. The tissue concentration of VIP measured by immunochemistry was in good agreement with the immunohistochemical findings. VIP inhibited the spontaneous smooth muscle activity in strips from the Fallopian tube and the cervical region, but had no effect on strips from the uterine corpus. The data support the view that VIP may play a physiological role in the local controlof smooth muscle motility in the human

THE EFFECT OF RESERPINE UPON THE RATE OF EGG TRANSPORT IN THE FALLOPIAN TUBE OF THE MOUSE

Reserpine is a tranquillizer and hypotensive agent (Plummer, Earl, Schneider, Trapold & Barret, 1954) which has been shown to influence uterine smooth muscle activity (Clegg, 1963). The present study was undertaken to investigate the effects of reserpine upon the rate of transport of eggs down the Fallopian tube of the mouse. A stock solution was made by dissolving 300 mg reserpine and 375 mg citric acid in 6 ml benzyl alcohol with gentle warming. A volume of 15 ml of Tween 80 was added. After cooling, the final volume was adjusted to 100 ml with distilled water, and the solution protected from light. This reserpine stock solution was diluted with distilled water immediately before use to adjust the dose volume to 10 ml/kg body weight. Specific pathogen-free mice were obtained from colonies in our laboratories. Pregnant female mice were killed on a defined day of pregnancy after dosing with reserpine and the reproductive tract removed, the morning on which the vaginal plug was observed being designated the 1st day of pregnancy. The Fallopian tubes were straightened and mounted in normal saline. The contained eggs were visible within the tube (Pl. 1, Fig. 1). Since back and forth movement of the eggs was of very low frequency immediately after mounting, the positions of the first and last eggs could be measured together with the total length of the tube, using a moving-stage microscope with a vernier scale. The percentage of the tube length travelled by the first and last eggs was calculated from the measurements obtained; the mean values were taken to indicate the position of the centre of the group of eggs. The uterine horns were flushed with normal saline and the recovered eggs counted. In a preliminary study, varying dose levels of reserpine were administered by intraperitoneal injection on the 1st day of pregnancy, using a dose ratio of 2\m=.\0.