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Biomedical subjects

B Ottesen

Publications and source records attributed to B Ottesen.

At least 109 records · Page 6Linked to original sources
PubMed1981

Mechanism of action of vasoactive intestinal polypeptide on myometrial smooth muscle of rabbit and guinea-pig.

1. The action of vasoactive intestinal peptide (VIP) on the electrical and mechanical activity of strips of longitudinal myometrial smooth muscle from rabbits and guinea-pigs treated with oestradiol was studied in the sucrose-gap apparatus. 2. In myometrial strips which spontaneously exhibited regular contractions, or which were induced to contract rhythmically to the application of oxytocin, VIP reduced both the frequency and the force of contraction. 3. Contractions were associated with bursts of action potential discharge. In guinea-pig, the membrane potential reached its most negative value shortly following a burst and a slow decay of negativity followed ("generator potential'). VIP inhibited the decay of this negativity and increased the duration of the period between bursts. In rabbit myometrical strips, electrical discharges occurred less regularly but VIP also had an inhibitory action. The inhibitory action of VIP was not affected by the beta-adrenoreceptor blocker propranolol, by tetrodotoxin, or by apamin. 4. Using the double sucrose-gap apparatus, bursts of action potentials and contractions were elicited with depolarizing electrical pulses in the absence of oxytocin. Changes in membrane resistance were also estimated by eliciting hyperpolarizing electrotronic potentials. VIP hyperpolarized the membrane and inhibited contractions as depolarizing pulses now failed to reach threshold for action potential discharge or fewer action potentials were discharged. A small (about 10%) reduction in membrane resistance was freqeuently observed during the hyperpolarization. 5. If a single action potential was elicited in the presence of VIP, the tension generated by the muscle was less than in its absence. 6. In a calcium-free high-potassium (126 mM) solution, readmitting calcium produced contraction; VIP inhibited this contraction. Activation of beta-receptors by means of isoprenaline had a similar effect but unlike isoprenaline the action of VIP was not blocked by propranolol. 7. It is suggested that the primary action of VIP is on the calcium economy of the myometrial smooth muscle cell, possibly to accelerate sequestration and/or extrusion of calcium from the cell. In some way this is associated with inhibition of the generator potential, hyperpolarization, and with a small increase in permeability of the membrane to potassium.

Action Potentials↗
PubMed1981

Distribution and motor effect of VIP in female genital tract.

The distribution and concentration of vasoactive intestinal polypeptide (VIP) in different parts of the female genital organs from various species (cat, goat, pig, rabbit, rat, and guinea pig) were studied by means of immunohistochemistry and immunochemistry. In addition, the effect of VIP on the mechanical activity of uterine muscle was investigated in vitro. VIP immunoreactive nerve fibers innervating vessels and smooth muscle cells were fairly numerous in the genital organs of the cat and goat and less numerous in the pig, rabbit, rat, and guinea pig. In all species studied, VIP-containing nerves were most numerous in the cervix. The tissue concentration of VIP measured by immunochemistry was in agreement with the immunohistochemical findings. VIP inhibited the mechanical uterine activity in the cat, goat, pig, and rabbit, whereas only minimal effects were obtained in the rat and guinea pig. This difference between the species corresponded to the number of VIP-containing nerves in the uterine muscle. The data support the hypothesis that VIP may play a physiological role in the local nervous control of the uterine mechanical activity.

Animals↗
PubMed1981

Vasoactive intestinal polypeptide (VIP) in the male genitourinary tract: concentration and motor effect.

Vasoactive intestinal polypeptide (VIP) has previously been shown in nerves of the male and female genitourinary tract, appearing to innervate vascular and nonvascular smooth and epithelial cells. In the present study the concentration of VIP in tissue extracts of different parts of the male genitourinary tract from cat and man was determined by radioimmunoassay. In addition, the effect of VIP on the contractility of the smooth muscle from the cat genitourinary tract was investigated in vitro. The tissue concentrations of VIP were generally higher in cat than in man. In both species high concentrations were found in the vas deferens, bladder, urethra and prostate, In concentration from 3 x 10(-8) to 6 x 10(-7) mol x 1-1, VIP inhibited in a concentration-dependent manner the muscle contractions in specimens from all regions examined, i.e., the vas deferens, ureter, corpus of the bladder, and urethra. The data indicate that VIP might play a physiologic role in the local nervous control of the smooth muscle activity in the male genitourinary tract.

Adult↗
PubMed1980

Vasoactive intestinal polypeptide (VIP) inhibits prostaglandin-F2 alpha-induced activity of the rabbit myometrium.

Seven female rabbits ahd myometrial autografts transplanted into ear-chambers. The electrical activity of the graft was recorded and mechanical activity observed. Vasoactive intestinal polypeptide (VIP) dose-dependently inhibited myometrial activity induced by prostaglandin-F2 alpha. This evidence and the occurrence of "VIPergic" nerve fibres, which seem to innervate the myometrial cells, suggest that VIP may play a physiological role in the local control of the myometrial activity.

Animals↗
PubMed1980

Measurement of myometrial blood flow in rabbits by washout of xenon-133 after atraumatic local labelling.

In vivo experiments were performed on the uterine tissue of non-pregnant estradiol treated rabbit anesthetized with sodium pentobarbitone. The average blood flow calculated from the washout of Xenon-133 after atraumatic labelling from the uterine surface was 25.4 ml . min-1.(100 g)-1 (range 7.4-66.6), and after local injection of a tracer in isotonic saline directly into the myometrium 24.4 ml.min-1.(100 g)-1(range 8.7-45.3). During the experiments a monoexponential washout curve was found for the whole washout process both after atraumatic labelling and when the injected volume was 5 microliter. No trauma of injection was observed using this injection volume. The results support the applicability of a monocompartmental model for the washout of inert gas from the myometrium. Thus myometrial blood flow can be calculated from the Xenon-133 washout rate at any time interval during the washout process.

Animals↗
PubMed1980

Effects of VIP in the female genital tract.

Vasoactive Intestinal Polypeptide (VIP) has been demonstrated in the female genitourinary tract, localized in neurons which seem to innervate vessels and non-vascular smooth muscle. The present work has demonstrated that the concentration of immunoreactive VIP varies between different mammalian species and within the genital tract of the same species. Using various in vivo and in vitro preparations the peptide was found to have a dose-dependent inhibitory effect on the myoelectrical activity and contractility of the uterine muscle, and to increase myometrial blood flow. The findings support the hypothesis that VIP may play a physiological role in the local control of uterine motility and blood flow.

Animals↗
PubMed1980

Vaginal blood flow during sexual stimulation.

In 7 female volunteers the local vaginal blood flow was calculated from the washout of the radioactive inert gas xenon 133 after an intraepithelial injection. During rest a monoexponential washout curve was found for the whole washout process. The average vaginal blood flow (VBF) was found to be 9.8 ml.min-1. (100 g)-1 (range, 5.5 to 19.6). In 6 of the women when sexual stimulation was undertaken an increase in blood flow was recorded to an average of 28.9 ml.min-1. (100 g)-1 (range, 21.5 to 45.0).

Adult↗
PubMed1979

Plasma progesterone, serum estriol and plasma HPL determinations during the last trimester to detect changes before spontaneous labor. Comparison of progesterone assay using RIA and CPB.

Conflicting results have been published regarding changes in plasma progesterone during the last trimester of pregnancy. Some have demonstrated a fall in plasma progesterone before labor, and this has been taken as a possible explanation of the onset of labor. It has been suggested that the various results could be due to differences in methods for progesterone determination. In this study the progesterone levels were determined by both RIA and CPB. In 11 women the plasma progesterone, human placenta lactogen, and serum estriol were measured weekly during the last trimester of normal pregnancies and immediately after delivery. All samples were analysed radioimmunologically. In order to compare the radioimmunoassay and competitive protein binding techniques (RIA and CPB), the progesterone levels were determined by both methods. This was also done for 80 successive plasma progesterone routine samples drawn from women who were not pregnant or who were in the early stages of pregnancy. Both methods showed a significant rise in the plasma progesterone level during the last 6 weeks before spontaneous labor. However, the values obtained were lower when assayed by CPB than by RIA, presumably because of a higher specificity and a cross reaction in RIA. Serum estriol exhibited increasing values throughout pregnancy, but without a significant rise during the last few weeks. Plasma HPL settled at a constant level during the last few weeks before labor.

Estriol↗
PubMed1977

Glucose tolerance and insulin secretion in hyperthyroidism.

To evaluate the glucose tolerance and insulin secretion in hyperthyroidism patients were examined in the toxic state and after they had been made euthyroid. Fasting values: In 42 untreated patients the glucose- and insulin concentrations in serum were significantly elevated. In 24 treated patients the glucose concentrations became normal, while the insulin concentrations remained elevated. Oral-glucose-tolerance test: In 20 untreated patients the glucose- and insulin responses were significantly increased. In 8 treated patients the glucose response became normal, while the insulin response remained unchanged. Intravenous-glucose-tolerance test: In 28 untreated patients the K-values were significantly decreased and the insulin response increased. In 23 treated patients the K-values rose significantly, but the insulin response remained unchanged. Intravenous-tolbutamide test: In 41 untreated patients the glucose concentration decreased significantly compared with the controls, and the insulin responses were significantly increased. In 23 treated patients the glucose concentrations decreased even more, while the insulin response remained unchanged. The results indicate enhanced sensitivity or an increase in the mass of beta-cells in hyperthyroidism. The glucose tolerance tests point to an increased peripheral insulin resistance. The normalized glucose tolerance and still enhanced insulin secretion during treatment support the assumption, that hyperthyroidism causes an increase in the beta-cell mass.

Administration, Oral↗
PubMedDate not supplied

Multiplicity of receptors for vasoactive intestinal polypeptide (VIP): differential effects of apamin on binding in brain, uterus and liver.

Apamin is a neurotoxic octadecapeptide from bee venom, which has been shown to inhibit the non-adrenergic, non-cholinergic inhibitory innervation of the smooth muscle of the gut. Since vasoactive intestinal polypeptide (VIP) has been proposed as a possible inhibitory neurotransmitter, the effect of apamin on the receptor binding of 125I-VIP was studied using the following assays: (1) isolated synaptosomes from rat cerebral cortex, (2) crude plasma membranes from hog uterine smooth muscle, and (3) purified plasma membranes and isolated hepatocytes from hog liver. Apamin inhibited the receptor-bound 125I-VIP on membranes from brain or myometrium, although the binding affinity was 100-1000 times lower than for VIP. The displacement curves for VIP and apamin were parallel suggesting that apamin interacts with both the low and high affinity VIP receptors. In membranes and cells from liver, apamin was unable to displace receptor-bound 125I-VIP in concentrations up to 50 mumol/l. The findings suggest that the VIP receptors in liver are different from those in the brain cortex and myometrium.

Animals↗
PubMedDate not supplied

Neuropeptides in the female genital tract: effect on vascular and non-vascular smooth muscle.

The presence of vasoactive intestinal polypeptide (VIP), substance P (SP), somatostatin, enkephalin, and avian pancreatic polypeptide (APP) in nerves in the female genital tract raises the question of their physiological significance as neurotransmitter substances. We have examined the effect of these peptides on non-vascular uterine smooth muscle in vivo as well as in vitro, and the effect on blood flow in the genital tract of rabbit and cat. SP caused a dose-dependent increase in mechanical and myoelectrical activity, an action which could be antagonized by VIP. Substance P, leu-enkephalin and VIP induced a concentration related increase in blood flow of the uterus, where VIP seems to be the most potent vasodilator. Neither the effects on vascular nor on non-vascular smooth muscle were inhibited by adrenergic nor cholinergic blocking agents. APP was able to inhibit the VIP-induced vasodilation in rabbits. These findings suggest that several peptides are involved in the local nervous control of both uterine contractions and haemodynamic events.

Animals↗
PubMedDate not supplied

Insulin receptors in rat brain cortex. Kinetic evidence for a receptor subtype in the central nervous system.

Binding kinetics of porcine 125I-insulin were studied in synaptosomal and microsomal fractions of rat brain cortex. Receptor binding was temperature- and pH-dependent with optimum at 4 degrees C and pH 8.0-8.3. At 15 degrees C, steady state binding was heterogenous, and Scatchard analysis revealed two classes of receptors with Kd of 2 nmol/l and 40 nmol/l in amounts of 50 pmol/g and 200 pmol/g of membrane protein. Dissociation kinetics were biexponential with T1/2 of about 5 min and 180 min, and in contrast to other cell-types, not influenced by negative cooperativity. No receptor-mediated insulin degradation was detectable at 37 degrees C in the presence of bacitracin. Insulin analogues inhibited 125I-insulin binding with potencies relative to porcine insulin (%): human insulin 100, rat insulin (I + II) 71, coypu insulin 47, rat multiplication stimulating activity 8, porcine proinsulin 5, among which the three last values were significantly higher than in rat liver and fat cells. No competition was observed with porcine relaxin and mouse nerve growth factor up to about 1 mumol/l. Receptors were present in all regions of central nervous system with highest concentrations in the cerebral cortex, cerebellum and olfactory bulb, and lowest in the pons, medulla oblongata and spinal cord. In conclusion, insulin receptors in rat brain cortex are functionally different from other tissues regarding the insulin specificity and the absence of negative cooperativity. It is suggested that an insulin receptor subtype in rat brain mediates the growth activity of insulin on nerve cells.

Animals↗
PubMedDate not supplied

VIP receptors in pig liver cells: binding characteristics and role in degradation.

The physiological role of VIP in the liver is controversial. VIP receptors are present, but their function in the metabolic regulation is uncertain. The interaction of porcine VIP with isolated cells from pig liver was studied with respect to receptor-binding, degradation and glycogenolytic action. In this model, VIP and liver showed homology of animal species. 1. Receptor-binding was heterogenous with Kd values of 10(-9) mol/l and 4 X 10(-8) mol/l, and a total amount of binding sites of 7 X 10(-11) mol per 10(9) cells. The peptide specificity showed that porcine and chicken VIP were equally potent in inhibiting receptor-bound 125I-VIP; secretin was about 30 times less potent; glucagon and somatostatin were ineffective. 2. Receptor-bound 125I-VIP was degraded since about 70% was released as radioactivity not reacting with VIP-antiserum. 3. Glucose-release was not stimulated by VIP (10(-6) mol/l) whereas the rate was increased two-fold by glucagon (10(-6) mol/l). In conclusion, VIP receptors in pig liver cells are different from other tissues regarding peptide specificity. It is suggested that receptor-binding mediates degradation of VIP by pig liver rather than metabolic effects.

Animals↗
PubMedDate not supplied

Vasoactive intestinal polypeptide (VIP) provokes vaginal lubrication in normal women.

The human vagina is known to be heavily innervated by vasoactive intestinal polypeptide (VIP) immunoreactive nerve fibres. In the present study we have examined the effect of VIP (900 pmol x kg-1 x h-1, IV during 30 min) on vaginal lubrication and blood flow in fourteen normal non-pregnant women. Vaginal blood flow was measured by the heat clearance technique and the vaginal lubrication quantified by the weight gain of preweighed filter papers placed on the surface of the vaginal wall for 30 min. Arterial blood pressure, pulse frequency and the concentration of VIP in peripheral blood were monitored. VIP (median concentrations of 200-300 pmol x l-1) induced a significant increase in vaginal blood flow accompanied by a 100% increase in vaginal lubrication (from 27 mg/cm2 to 53 mg/cm2). The VIP infusion lead to a significant increase in pulse frequency and a significant fall in diastolic arterial blood pressure. The findings suggest that VIP may participate in the control of the local physiological changes observed during sexual arousal: genital vasodilation and increase in vaginal lubrication.

Adult↗
PubMedDate not supplied

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.

Animals↗
PubMedDate not supplied

Interaction of NPY and VIP in regulation of myometrial blood flow and mechanical activity.

The occurrence, molecular characteristics and biological function of neuropeptide Y (NPY) has been studied in the female genital tract of non-pregnant rabbits. NPY immunoreactivity was demonstrated throughout the genital tract. Maximum concentrations were found in the salpinx (fallopian tube), 570 pmol/g (median) lower within the uterine body (1.5 pmol/g), cervix (2.8 pmol/g) and vagina (3.6 pmol/g). In vitro, NPY had a dose-dependent stimulatory effect on non-vascular smooth muscle (ED50 10(-9) mol/l) as studied by myometrial tension recordings. In vivo, NPY (50 pmol/min.kg) induced a dose-related, non-adrenergic and non-cholinergic decrease in myometrial blood flow. Small C-terminal (NPY31-36) or N-terminal (NPY1-16) fragments of NPY had no effect on myometrial blood flow. NPY was found to interact with the smooth muscle effect of VIP; the presence of VIP (10(-8) mol/l) counteracted the contraction elicited by NPY (10(-8) mol/l) returning the response to control value. VIP and NPY displayed a similar physiological antagonism on myometrial blood flow. There was a clear difference in the response to VIP and NPY as the effect of NPY on myometrial blood flow first appeared after a lag period of 2 minutes whereas the effect of VIP was almost instantaneous. It is concluded that NPY and VIP may interact in the local nervous control of genital functions.

Animals↗
PubMedDate not supplied

Peptide histidine methionine (PHM) increases vaginal blood flow in normal women.

The effect of increasing doses of PHM given subepithelially or intravenously on vaginal blood flow was studied. Vaginal blood flow was measured by a heated oxygen electrode, and the concentration of PHM in peripheral plasma was monitored radioimmunochemically. Injection of PHM induced a significant dose-dependent increase in vaginal blood flow. The flow values correlated with the plasma concentrations independent of the way of administration. The efficacy was the same as previously found for VIP but the potency of subepithelially injected PHM was found to be 10-fold lower than that of VIP. In conclusion, PHM and VIP seem to have similar vasodilatory effects upon vaginal blood flow.

Administration, Intravaginal↗