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Biomedical subjects

R Ekman

Publications and source records attributed to R Ekman.

At least 253 records · Page 14Linked to original sources

Depletion of neuropeptides in rat parotid glands and declining atropine-resistant salivary secretion upon continuous parasympathetic nerve stimulation.

In rats the parasympathetic auriculo-temporal nerve on one side was continuously stimulated at 40 Hz for 20-80 min in the presence of adrenergic blockers (dihydroergotamine and propranolol) +/- atropine. During the first 10 min this gave rise to a flow of saliva from the parotid gland that in the atropinized rats amounted to 35% of that found in rats not treated with atropine, while the protein and amylase outputs were 75% of those in non-atropinized rats. The atropine-resistant secretion of fluid and proteins declined to 5-10% of the initial value within 40 min but did not cease completely even after 80 min. The marked reduction in secretory responses was not due to desensitization or exhaustion of the gland cells. The nerve stimulation reduced the parotid gland content of vasoactive intestinal peptide (VIP) and substance P (SP) to approximately 60 and 25% of that of contralateral glands after 20 and 60 min, respectively. The probable explanation for the decline in secretory response seems to be depletion of non-adrenergic, non-cholinergic transmitter(s). The present results suggest that neuropeptides are involved in the regulation of salivary secretion but provide no direct evidence that either VIP or SP is responsible for the atropine-resistant salivary secretion.

Amylases↗

PYY-like peptides in the central and peripheral nervous system of a frog and a lizard.

PYY-immunoreactive material was detected in endocrine cells in the gut of a lizard, Lacerta vivipara, and a frog, Rana temporaria. The findings are consistent with other reports on reptiles, amphibians and higher species. In addition, however, PYY-like material was found in neuronal elements both in the gut and in the brain. High performance liquid chromatography of frog brain extracts showed the PYY-like material to elute in one minor fraction (eluting position similar but not identical to that of porcine synthetic PYY) and two major fractions (distinct from PYY and probably representing smaller and more hydrophobic PYY-like peptides).

Animals↗

Two distinct VIP precursors in cartilaginous fish?

In the ray gut immunoreactive VIP has a dual localization in endocrine cells and in nerve fibers. Immunoreactive VIP and PHI were found to co-exist in the same nerve fibers. This is predictable, since VIP and PHI derive from the same precursor. However, PHI could not be demonstrated in the VIP immunoreactive endocrine cells. Chromatographic analysis (high performance liquid chromatography) of extracts of the gut revealed two different molecular forms of VIP, one large peak with an elution position similar to that of authentic porcine VIP and a minor peak with a different elution position. The results suggest either the existence of different precursors for VIP in endocrine cells and in neurons, or the different processing of the same precursor in neurons and endocrine cells.

Animals↗

Delta-sleep inducing peptide in cerebrospinal fluid from schizophrenics, depressives and healthy volunteers.

CSF levels of DSIP was measured in healthy volunteers and in hospitalized patients with schizophrenia or major depressive disorders. Both patient groups had significantly lower CSF levels of DSIP than the healthy volunteers. There was a tendency for lower CSF levels of DSIP in female compared to male schizophrenics. Neuroleptic treatment did not significantly affect those levels. The levels of DSIP in CSF tended to be inversely correlated to the sleep disturbancy scores in the depressed patients.

Adolescent↗

Binding of estrogen and progesterone to human endometrium in the different phases of the menstrual cycle. A histochemical study.

Specific estrogen and progesterone binding in human endometrium was studied histochemically using fluorochrome-labeled steroids (estradiol-17 beta-BSA-FITC and progesterone-BSA-TMRITC), endometrial samples from 36 women being investigated. The binding pattern was similar with both reagents. The relationship between the bindings to glands and to stroma, however, varied with the menstrual phase of the tissue. The specific fluorescence was more intense in the epithelial structures in the proliferative phase. In the secretory phase, the fluorescence from stromal cells was as intense as, or more intense than, that from the glands. The localization of the fluorophores in the glandular epithelial cells also varied by menstrual phase. In the proliferative phase, the fluorescence was most intense in the basal part or the whole cytoplasm of the glandular epithelial cells, while in the secretory phase the fluorescence was most intense in the apical and sometimes also in the basal part of the epithelial cells.

Adult↗

Levels of neural vasoactive intestinal polypeptide in rat uterus are markedly changed in association with pregnancy as shown by immunocytochemistry and radioimmunoassay.

Immunocytochemical studies have shown that the rat uterus is well innervated by nerve fibers containing vasoactive intestinal polypeptide (VIP). The fibers were associated with both vascular and nonvascular smooth muscle cells, and they were somewhat more numerous in the cervix compared to the uterine horns. This was confirmed in radioimmunologic determinations. Pregnancy induced a marked, almost 50% reduction in the total content of VIP in the uterine horns, which was associated with an almost complete disappearance of immunocytochemically visible nerve fibers in this part of the uterus. The innervation normalized within 25 days following delivery. Less marked changes occurred in the VIP innervation of the cervical region, where the concentration of the peptide was reduced mainly as a result of the increased tissue weight during pregnancy.

Animals↗

Establishment and characterization of cell lines from human small cell and large cell carcinomas of the lung.

Five new small cell carcinomas (SCC) cell lines and a large cell carcinoma (LCC) cell line were established from human lung cancers. The SCC cell lines had, as a group, common phenotypic properties which distinguished them from non-SCC cell lines. However, the studies also revealed a considerable biological heterogeneity among the individual SCC cell lines. Thus, the SCC cell lines had a typical growth pattern with cell clusters in suspension or partly adherent to the bottom. All the lines examined grew in agarose with variable cloning efficiencies, and all but one line formed tumors subcutaneously in nude mice. The ultrastructure of the SCC cell lines was characteristic with dense core granules at a variable frequency. Neuron-specific enolase was detectable in all SCC cell lines, usually in large amounts, and an inconstant production of a spectrum of polypeptide hormones was found, typical of SCC. The LCC cells proliferated in monolayers, formed colonies in agarose and grew in nude mice. Ultrastructurally, the LCC cell line differed from the SCC cell lines in having intra- and intercellular lumina and tonofilaments. The capacity of the LCC and a previously established squamous cell carcinoma cell line (U-1752) to produce neuron-specific enolase and polypeptide hormones was characteristically much lower than that of the SCC cell lines. We conclude from this study that SCC cell lines, although individually distinct from one another, are quite homogeneous as a group in expressing a set of basic common neuro-endocrine markers. However, these studies also suggest some biological relationship between SCC, LCC and SQC by virtue of their expression of some common neuro-endocrine markers, in support of the concept of a common histogenetic origin of human lung cancers.

Carcinoma, Small Cell↗

Changes in oviductal VIP content induced by sex steroids and inhibitory effect of VIP on spontaneous oviductal contractility.

The content of vasoactive intestinal polypeptide (VIP) in rabbit oviducts was determined using a radioimmunoassay technique. Treatment with oestrogen (polyestradiolphosphate) alone for 5 days caused a significant increase in oviductal VIP content, whereas addition of progesterone during the last 3 days of an 8 day polyestradiol-phosphate treatment resulted in a return of VIP content to control levels. The effect of VIP on oviductal smooth muscle contractility was investigated using an in vitro system. It was found that VIP caused a reduction of spontaneous contractile activity in doses as low as 10(-10) M and this reduction in motor activity was strictly dose dependent with an ED50 value similar to that reported for the VIP activity on rabbit myometrial smooth musculature.

Animals↗

Glucagon and VIP in the retina.

Immunoreactive glucagon and immunoreactive vasoactive intestinal polypeptide (VIP) have been demonstrated in neuronal elements in the retina of a number of species by immunohistochemistry. In the present study, the concentrations of glucagon-like and VIP-like material in retinae from different species were determined by radioimmunoassay. The retinal concentration of glucagon-like immunoreactivity was 10-35 pg/mg in goldfish, chicken, pigeon, and frog, whereas retinae from cow, pig, rabbit, and rat contained very little. Retinae from the latter four species were on the other hand rich in VIP-like material whereas retinae from cat, guinea pig, and goldfish contained very little. The glucagon-like immunoreactive material in chicken and frog retina was subjected to gel chromatography and high performance liquid chromatography (HPLC). The results indicate that the extracted protein is of similar molecular size as porcine pancreatic glucagon, distinct from porcine glicentin. VIP immunoreactive material extracted from bovine retina was similar in molecular size as authentic porcine VIP by gel chromatography.

Animals↗

Neuronal cholecystokinin, gastrin-releasing peptide, neurotensin, and beta-endorphin in the intestine of the guinea pig. Distribution and possible motor functions.

The guinea-pig intestine was found to harbor nerve fibers containing immunoreactive cholecystokinin (CCK), gastrin-releasing peptide (GRP), neurotensin or beta-endorphin. Such fibers occurred in the myenteric and submucous ganglia and in the smooth muscle. GRP- and CCK-fibers, in addition, were found in the mucosa. Following colchicine treatment, neuronal perikarya in the myenteric ganglia displayed CCK-, GRP-, or beta-endorphin immunoreactivity. CCK-immunoreactive perikarya were located also in the submucous ganglia. Neurotensin-immunoreactive cell bodies could not be detected. The presence of immunoreactive neuronal perikarya in intramural ganglia indicates that CCK-, GRP- and beta-endorphin-containing fibers are intrinsic to the gut wall. GRP, neurotensin, and beta-endorphin were identified in extracts of smooth muscle by immuno-chemical and chromatographic analysis. CCK-8, GRP and neurotensin contracted the isolated taenia coli. Tetrodotoxin reduced the response to CCK-8 but not that to GRP and neurotensin, suggesting that the two latter peptides act directly on smooth muscle receptors. The effect of CCK-8 is partly mediated by cholinergic nerves, since not only tetrodotoxin but also atropine greatly reduced the CCK-8-induced contractile response. The substance P (SP) antagonist, (D-Pro2, D-Trp7,9)-SP1-11 had no effect on the CCK-8-induced contraction of the taenia. CCK-8 enhanced the SP-mediated (atropine-resistant) contractile response to electrical stimulation but not that mediated by acetylcholine. beta-Endorphin had no effect on the tension of the muscle but reduced the response to electrical stimulation (cholinergic as well as SP-mediated) through a naloxone-sensitive mechanism. While CCK-8 and beta-endorphin seem to play neuromodulatory roles in the taenia coli, the significance of GRP and neurotensin remains enigmatic.

Animals↗

Novel variants of adrenocorticotrophic hormone in porcine anterior pituitary.

Extracts of porcine anterior pituitary contain several corticotrophic variants of ACTH 1-39. They were isolated by adsorption chromatography, ion-exchange chromatography and reverse-phase high-performance liquid chromatography. Four variants were then identified as starting and ending at positions corresponding to ACTH 1-38, 1-37, 7-39 and 7-38. Several of these fragments were recovered in chromatographically multiple forms. Although all fragments isolated had corticotrophic activity (measured on isolated rat adrenal cells) those with a shortened N-terminal region had a lower potency than those with an intact N-terminal region. Corticotrophic activity of porcine ACTH 7-38 was detected in a preparation with a beta-aspartyl shift at position 25. However, in agreement with previous studies, synthetic human ACTH 7-38, in which an intact Asn-Gly bond was structurally proven, possessed no such activity. The results indicate that position 25 as well as positions 1-6 are important for corticotrophic activity, and that a deamidative beta-aspartyl shift at position 25 can influence the activity.

Adrenal Glands↗

Vasoactive intestinal peptide and substance P in salivary glands of the rat following denervation or duct ligation.

Immunoreactive vasoactive intestinal peptide (VIP) and substance P (SP) were studied in parotid, submaxillary and sublingual glands of the rat. The concentration of VIP was highest in the submaxillary gland and lowest in the parotid gland. The concentration of SP was highest in the parotid gland; it was at, or below the limit of detection in the sublingual gland. In the parotid gland the total amounts of VIP and SP were reduced by 95% after parasympathetic denervation (section of the auriculo-temporal nerve). In the submaxillary gland the total amounts of the peptides were unchanged after parasympathetic decentralization (section of the chorda-lingual nerve). In this gland the total amount of SP was reduced by 92% and that of VIP by 50%, when the chorda tympani nerve fibres were cut deep into the hilum. Cutting the nerve fibres at the hilum left the total amounts of the peptides unchanged in the submaxillary gland, whereas in the sublingual gland the total amount of VIP was reduced by 70%. Sympathetic denervation did not reduce the total amounts of the peptides. Duct ligation caused gland atrophy. In the parotid gland the total amounts of VIP and SP were reduced by 40%. In the submaxillary gland the same percentage reduction occurred with regard to SP; however, the total amount of VIP was reduced by 99%. The VIP- and SP-containing nerve fibres reach the salivary glands by the parasympathetic nerves. In both submaxillary and sublingual glands a certain fraction of VIP originates within the glands.

Animals↗

GRP neurones in the rat small intestine issue long anal projections.

Gastrin releasing peptide (GRP) immunoreactive nerve fibres are numerous in the gut wall. Nerve cell bodies containing GRP are regularly found in the myenteric ganglia. The projections of GRP neurones in the rat small intestine were studied after myectomy or transection of the gut wall. Operated rats were left for 8-10 days or 5 weeks. Specimens were studied by immunocytochemistry, immunochemistry and in vitro for motor activity. GRP fibres were absent and GRP was markedly reduced in the gut wall underlying the area of myectomy and 10 mm anally to the myectomy or site of transection. Further anally, GRP and the GRP fibres gradually returned and were back to normal 25-30 mm from the lesion. Myenteric GRP neurones in the rat small intestine thus project anally over a distance of approximately 20-25 mm. A series of experiments was performed in order to test the idea that GRP is directly involved in intestinal motor functions. The results did not support this view. Strips of longitudinal smooth muscle with adherent myenteric ganglia were taken orally and anally to the myectomy and the motor activity of the specimens was compared. Electrical stimulation evoked a contractile response in the oral segment that was 6 times greater than that of the anal segment. However, GRP (10(-9)-10(-5) M) did not evoke contraction and the electrically induced contractile response was unaffected by GRP but could be blocked by atropine. The reduced contractile response in the 'denervated' anal segment is thus probably not due to a shortage of GRP fibres.

Animals↗

Continuous infusion of somatostatin evokes escape of gastric acid inhibition in the rat.

In rats with chronic gastric fistula, constant infusion of somatostatin failed to maintain a sustained inhibition of basal and pentagastrin-stimulated gastric acid secretion for greater than 4-6 h. After 8-12 h, the secretion was back to the level observed before infusion of somatostatin. The desensitization seemed specific in that infusion of secretin at this stage inhibited the secretion. After interruption of an 18-h-infusion, the responsiveness to somatostatin returned gradually; it was completely restored at 2 h. In marked contrast, intermittent administration of somatostatin produced a sustained pulsatile response pattern of the pentagastrin-stimulated acid secretion over a period of 18 h, the rhythm selected being 20 min of somatostatin + pentagastrin infusion followed by 40 min of pentagastrin alone. The desensitization to somatostatin is of particular interest in view of the postulated paracrine nature of the somatostatin cells in the stomach.

Animals↗

Radioimmunoassay of delta sleep-inducing peptide using an iodinated p-hydroxyphenylpropionic acid derivative as tracer.

A highly sensitive radioimmunoassay for delta sleep-inducing peptide (DSIP) has been developed. A p-hydroxyphenylpropionic acid conjugate of DSIP was used for radioiodination. Using reversed-phase high performance liquid chromatography the labelled DSIP derivative was isolated in a high yield and with a high specific activity. The assay allows measurement of DSIP-like material in body fluids with a minimum detectable concentration of 0.1 ng/ml standard DSIP (10 pg/tube).

Delta Sleep-Inducing Peptide↗

Neuronal gastrin-releasing peptide in the mammalian gut and pancreas.

Immunoreactive gastrin releasing peptide (GRP) was demonstrated in neuronal elements in the porcine pancreas and in the gut of several mammals. Immunoreactive endocrine cells could not be detected. The results of radioimmunochemical analysis agreed well with those of immunocytochemistry. The occurrence of gastrin-releasing peptide-containing nerve cell bodies in the myenteric ganglia all along the gut indicates that gastrin-releasing peptide fibers are intramural in origin. The distribution of gastrin-releasing peptide fibers in all layers of the gut wall suggests multiple functions of gastrin-releasing peptide, including a role in the regulation of intramural neuronal activities, smooth muscle tone and in secretory and absorptive processes.

Animals↗

Tri-iodothyronine and thyroxine in human milk.

The concentration of tri-iodothyronine (T3) and thyroxine (T4) in human milk was determined by radioimmunoassay (RIA). The analysis of T3 was performed on unextracted milk and on ethanol extracts of defatted milk. Analysis of unextracted milk was complicated by artifacts. Reliable and reproducible results were achieved only with the milk extracts. In 10 colostral milk samples the mean T3 levels +/- SD were 0.80 +/- 0.52 nmol/l before feeding (early milk) and 0.93 +/- 0.62 after feeding (hind milk). The T3 concentration in colostrum did not change significantly during the feeding to the infant. In 12 mature milk samples collected between infant feedings, the mean T3 +/- SD was 1.19 +/- 0.42 nmol/l. T4 was not detected in any of the samples analysed (detection limit 3 nmol/l).

Colostrum↗