PubMed Health⌕ Search

Biomedical subjects

B Ottesen

Publications and source records attributed to B Ottesen.

At least 73 records · Page 4Linked to original sources

Preferential release of oxytocin in response to vasoactive intestinal polypeptide in rats.

Vasoactive intestinal polypeptide (VIP) was infused into the aorta of pentobarbitone-anesthetized rats (n = 12) in stepwise increasing doses of 0.001 to 10 micrograms/rat at rates varying from 0.3 pmol/min/kg to 3000 pmol/min/kg over 3 min. Blood was withdrawn from the vena cava inferior for the measurement of oxytocin (OT) and vasopressin (AVP) by RIA. The loss of blood was compensated for by infusion of isotonic saline (0.9% NaCl with 0.5% human serum albumin). Control rats received this solution only (n = 11). VIP infusions resulted in a dose-dependent increase in plasma OT which was significantly greater than the slight rise observed in the controls. The difference from controls was significant at infusion rates of 3 pmol/min/kg and more. Plasma AVP, on the other hand, did not rise in response to VIP infusions until the infusion rate was increased to 300 and 3000 pmol/min/kg. At these infusion rates, the increments in AVP were much smaller than those of OT, the levels during the highest infusion rates rising to 8.6 +/- 2.8 and 27.2 +/- 4.8 microU/ml, respectively (log normal means). The preferential release of OT in response to exogenous VIP in rats differs from the response in cats where intracarotid administration of VIP resulted in the release of proportionately more AVP than OT. Immunoreactive VIP is found in the hypothalamo-neurohypophyseal system of rats in close proximity of some of the magnocellular neurons as well as within the nerve terminals. This, together with our data, suggests that endogenous VIP may participate in the release mechanism for OT in rats.

Animals↗

Occurrence of VIP and peptide HM in human pancreas and their influence on pancreatic endocrine secretion in man.

By immunohistochemistry it was found that VIP- and peptide HI/peptide HM (PHI/PHM)-like immunoreactivity occurred in autonomic neurons in the human pancreas. Antisera against both VIP and PHI/PHM reacted with neuronal cells in local ganglia and these ganglia also contained PHI/PHM- and VIP-immunoreactive fibre plexuses. VIP- and PHI/PHM-positive fibres were also seen close to the Langerhans' islets. In addition, PHI/PHM- but not VIP-like immunoreactivity was observed in the endocrine cells often located in the periphery of the islets. The nature of these PHI/PHM-positive cells remains to be established. I.v. infusion of VIP at constant rates of 300 and 900 pmol/kg X h for 30 min in 6 healthy volunteers resulted in plateau values of 102 +/- 26 and 291 +/- 25 pM, respectively. These levels of VIP which are above those found in the circulation under physiological conditions stimulated secretion of insulin, C-peptide and pancreatic glucagon dose-dependently. On the contrary prolonged (60 min) infusion of PHM in doses resulting in plasma levels up to 1340 +/- 405 pM had no effect on pancreatic hormone secretion. These findings suggest that VIP is a likely neurotransmitter in the control of endocrine pancreatic secretion while PHM has a less prominent role, if any.

Adult↗

Vasoactive intestinal polypeptide concentration in human bladder neck smooth muscle and its influence on urodynamic parameters.

Three human studies were performed to evaluate the influence of vasoactive intestinal polypeptide (VIP) on bladder and urethral function. Bladder neck smooth muscle biopsies were obtained from nine men with functional bladder neck obstruction, from 10 men with medium sized benign prostatic hypertrophy and from four patients with a normal infravesical outlet. The biopsies were analysed for VIP by radioimmunoassay and by immunohistochemistry. No differences were found between the groups. Pressure-flow-EMG studies were performed in five men and urethrocystometry was performed in six women at rest, repeated coughing and at squeezing before, during and after VIP 3 micrograms/kg X h intravenously. No systematic changes developed in any of the urodynamic parameters.

Adult↗

Effect of vasoactive intestinal polypeptide (VIP) on steroidogenesis in women.

The VIPergic nervous system appears to be the major peptide-containing neuronal component in the female genital tract. Evidence has been put forward that exogenous VIP is able to stimulate progesterone secretion. In the present study the effect of human VIP (900 pmol/kg body weight per h i.v. during 30 min) on steroidogenesis in six female volunteers was investigated. The experiments were performed between the 6th and 14th day of their menstrual cycle, and peripheral venous blood was collected before, during and after infusion of VIP. The concentrations of VIP, oestradiol, progesterone, testosterone, androstenedione (AD), dihydrotestosterone (DHT), dehydroepiandrosterone sulphate (DHAS), sex hormone binding globulin (SHBG) and cortisol were measured. The infusion of VIP was accompanied by a 15% increase (P less than 0.05) in serum oestradiol concentrations, from a mean basal concentration of 0.58 nmol/l. The concentrations of testosterone and DHT also increased significantly. No effect of VIP on progesterone, AD, DHAS, SHBG or cortisol was observed. In the light of the presence of VIP in nerve fibres of the steroid producing tissue, this stimulatory effect of VIP might reflect a direct action on the ovary or the adrenal gland.

Adult↗

Release of vasoactive intestinal polypeptide (VIP) in breast-feeding women.

Blood samples were collected in peripheral venous blood of ten postpartum women before, during and after breast-feeding. Vasoactive intestinal polypeptide (VIP) and prolactin (PRL) were measured radioimmunochemically. A parallel significant increase in the VIP and PRL concentrations was observed following breast-feeding. VIP increased from a median control value of 4.5 pmol . 1(-1) to 18 pmol . 1(-1), and PRL increased from 2.8 U . 1(-1) to 5.2 U . 1(-1). A positive but insignificant correlation between corresponding PRL and VIP values was found.

Adult↗

VIP binding sites on synaptosomes from rat cerebral cortex: structure-binding relationship.

The structural requirements for VIP interaction with receptors on synaptosomes from rat cerebral cortex was investigated by the ability of VIP and VIP fragments, secretin analogues and fragments, peptides of the VIP/secretin family and several other regulatory peptides to inhibit specific 125I-VIP binding. Only large VIP fragments interacted with the VIP receptors with potencies relative to VIP ranging from 0.9-0.006%. The rank order of inhibition was: VIP 7-27 greater than VIP 11-28 greater than VIP 1-22-NH2 greater than VIP 16-28. Shorter fragments: VIP 18-28; VIP 18-28-NH2; VIP 19-28; VIP 21-28; VIP 22-28; VIP 1-18; VIP 1-18-NH2; VIP 1-10-NH2; VIP 1-6; VIP 16-20 and VIP 16-19 had no effect. Secretin fragments and analogues inhibited 125I-VIP binding with potencies of 2.2-0.01% relative to VIP in the order; secretin greater than (Ala4, Val5) secretin greater than (D-Ala4) secretin greater than (D-Phe6) secretin greater than secretin 5-27 greater than secretin 14-27. Other peptides of the VIP/secretin family inhibited 125I-VIP binding with potencies of 200-1%; avian VIP greater than porcine VIP greater than PHI = secretin greater than human GRF, whereas glucagon and GIP showed no inhibition. Among twenty-five other regulatory peptides only avian PP and somatostatin were inhibitors with relative potencies of 0.02% and 0.03%, respectively. In conclusion it may be emphasized that the intact VIP molecule is essential for VIP interaction with its receptors in the rat brain cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neurotransmitter-role of VIP in non-adrenergic relaxation of feline myometrium.

The feline myometrium is heavily innervated by VIP-containing nerve fibres. Transmural electrical stimulation (10 Hz, 2 msec, 150 mA) of muscle strips from feline myometrium in the presence of adrenoreceptor blocking agents caused a muscle relaxation. The smooth muscle relaxation was accompanied by a significant increase in immunoreactive VIP in the superfusate. Both the VIP release and the relaxation were completely annulled by tetrodotoxin, a selective blocker of axonal conduction. Furthermore, passive immunoneutralization with antiserum against VIP markedly reduced the smooth muscle relaxation induced by electrical stimulation. In the light of the previously demonstrated smooth muscle relaxant effect of VIP, the present findings indicate that the peptides may participate as neurotransmitter in non-adrenergic relaxation of the feline myometrium.

Animals↗

Peptides PHI and VIP: comparison between vascular and nonvascular smooth muscle effect in rabbit uterus.

The distribution and effects of the two neuropeptides, vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine amide (PHI), on vascular and nonvascular smooth muscle in the urogenital tract of nonpregnant rabbit female, were investigated. Immunoreactive VIP and PHI were present in all regions except the ovary with the highest concentration in the uterine cervix. By using in vitro tension recordings of myometrial specimens, it was demonstrated that both peptides displayed a dose-dependent inhibition of the mechanical activity. The dose-response curves of VIP and PHI were superimposable with and ID50 of 3 X 10(-8) mol/l, and their combined effect was additive. In addition, the influence of the two peptides on myometrial blood flow (MBF) was investigated by the xenon-133 washout technique. Both peptides were found to increase MBF with the same potency and efficacy. Their combined effect was additive. In conclusion VIP and PHI are present in the rabbit urogenital tract, and the two peptides are equipotent inhibitors of mechanical nonvascular and vascular smooth muscle activity in the uterus.

Animals↗

The regional distribution of receptors for vasoactive intestinal polypeptide (VIP) in the rat central nervous system.

The regional distribution of receptors for vasoactive intestinal polypeptide (VIP) was studied in the rat central nervous system (CNS). The specific binding was highest in cerebral cortex, limbic forebrain and cerebellum, whereas moderate to low binding was found in hypothalamus, thalamus, brainstem and pituitary. The lowest binding was observed in pons and spinal cord. Scatchard analysis showed curvilinear plots with upward concavity, which was interpreted as two classes of binding sites. The Kd values were similar in all regions and calculated as 2.4 and 62 nmol/liter, respectively. The variations of specific [125I]VIP binding were due to differences in the total amount of receptors and were in the range of 1.7-8.6 pmol per mg protein. The regional distribution of VIP receptors was parallel with the occurrence of VIP-containing nerve terminals with exceptions of cerebellum, olfactory areas and nucleus caudatus, where a greater number of receptors than expected from the VIP content was found. In these regions, VIP may interact with receptors for a different, but homologous neuropeptide. In conclusion, the regional distribution of VIP receptors in CNS gives further evidence for the role of VIP as a central neurotransmitter.

Animals↗

Influence of pregnancy and sex steroids on concentration, motor effect and receptor binding of VIP in the rabbit female genital tract.

The influence of sex steroid and pregnancy on the tissue concentration, uterine motor effect and receptor binding of VIP has been studied in the female genital tract of pregnant rabbits and oophorectomized rabbits during progesterone and/or oestrogen substitution. The concentration of immunoreactive VIP was high in the vagina and cervix, and lower in the uterine body of both pregnant and non-pregnant rabbits. A significant decrease in the VIP concentration (pmol/g wet weight) of the uterine body was observed toward term of pregnancy. The total uterine content of VIP, however, seems unchanged. Treatment of oophorectomized rabbits with ovarian steroids had no effect on the VIP concentration. The sensitivity for and potency of VIP on the relaxation of uterine muscle was significantly higher in oophorectomized rabbits treated with a combination of progesterone and oestrogen than in control rabbits. No difference was observed between non-pregnant and pregnant rabbits. The degradation and binding affinity for 125I-labelled VIP was highest in oophorectomized rabbits substituted with both oestrogen and progesterone. In the pregnant rabbits, the amount of receptors was decreased near term. In conclusion, sex steroids are able to influence the motor effect of VIP at the receptor level, but have no effect on the VIP concentration in the female genital tract.

Animals↗

Penile erection: possible role for vasoactive intestinal polypeptide as a neurotransmitter.

Concentrations of vasoactive intestinal polypeptide were measured in blood drawn from the cavernous spaces of corpus cavernosum of the human penis during tumescence and erection, and the effect of injecting the polypeptide into the cavernous spaces was studied. A significant release of the polypeptide was shown during tumescence and erection. Injection of exogenous vasoactive intestinal polypeptide induced erection. These findings support the concept of vasoactive intestinal polypeptide as a neurotransmitter in penile erection and suggest that it might have a clinical use in patients suffering from erectile dysfunction.

Adult↗

Vasoactive intestinal peptide (VIP) stimulates oxytocin and vasopressin release from the neurohypophyis.

The concentration of vasoactive intestinal peptide (VIP) was measured by RIA in pituitary extracts of female cats; it was significantly higher in the posterior than in the anterior lobe, 47.3 +/- 3.9 pmol/g wet wt vs. 7.7 +/- 2.0 pmol/g wet wt (mean +/- SE, n = 5 in both instances). To investigate the effect of VIP on the release of posterior pituitary hormones, the concentration of arginine vasopressin and oxytocin was measured by RIA in jugular vein plasma during intracarotid infusion of VIP. The levels of both hormones rose during the 5-min infusion of VIP. Oxytocin levels increased from a mean of 7.9 microU/ml to a maximum of 34.9 microU/ml at 1 min and arginine vasopressin levels from from 27.4 microU/ml to a maximum of 157 microU/ml at 1 min. The levels of both hormones returned to baseline values in about 20 min. Since VIP has been localized to the nerve terminals of the neurohypophysis, these data suggest that endogenous VIP may play a role as a neurotransmitter in the magnocellular hypothalmo-neurosecretory system.

Animals↗