Biomedical subjects

R Ekman

Publications and source records attributed to R Ekman.

At least 235 records · Page 13Linked to original sources

PubMed1987

Multiple tachykinin pools in sensory nerve fibres in the rabbit iris.

A population of sensory nerve fibres in the rabbit iris is known to contain calcitonin gene-related peptide and tachykinins, such as substance P and neurokinin A. In the presence of atropine and guanethidine, the isolated iris sphincter responded to electrical stimulation with a contraction that could be abolished by tachykinin antagonists. Capsaicin, known to release tachykinins from sensory fibres, evoked a long-lasting tachykinin-mediated contraction of the iris sphincter. Repeated application of capsaicin led to tachyphylaxis, possibly reflecting depletion of releasable neuronal stores of tachykinins. At this stage, electrical stimulation failed to elicit contraction. The capacity of capsaicin to release neuropeptides from sensory fibres was confirmed by determination of substance P- and calcitonin gene-related peptide-like immunoreactivity in the incubation medium and in the iris tissue. The concentrations of substance P and calcitonin gene-related peptide in the iris after capsaicin exposure were reduced by about 25%. Like capsaicin, bradykinin evoked a tachykinin-mediated contraction and tachyphylaxis. However, after development of tachyphylaxis to bradykinin, electrical stimulation or exposure to capsaicin still evoked tachykinin-mediated contraction, albeit a reduced one compared with the response before bradykinin. Hence, capsaicin completely depletes tachykinin stores releasable by prolonged electrical stimulation, whereas bradykinin exhausts only a sequestered pool. The possibility that tachykinins occur in several releasable pools in sensory nerves was investigated in yet another way: the iris sphincter muscle was stimulated electrically once every 2.5 min over several hours. The contractile response diminished gradually.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Calcitonin gene-related peptide and cerebral blood vessels: distribution and vasomotor effects.

The innervation of cerebral blood vessels by nerve fibers containing calcitonin gene-related peptide (CGRP) and the vasomotor effects of this peptide are described for a number of different mammalian species. CGRP-immunoreactive nerve fibers were present in the adventitia of cerebral arteries in all species examined (guinea pig, cat, rabbit, rat, and mouse). Numerous perikarya containing CGRP immunoreactivity are demonstrable in the trigeminal ganglion of all species. In the cerebral perivascular nerve fibers and in trigeminal perikarya, CGRP is often colocalized with substance P and neurokinin A. Marked interspecies differences exist both in the density of CGRP-immunoreactive nerve fibers and in the cerebrovascular levels measured with radioimmunoassay. The highest concentrations were observed in cerebral vessels from guinea pigs, the lowest concentration in rabbit vessels, and intermediate levels in the feline and human cerebral vasculature. CGRP is a potent dilator of cerebral arteries in all species examined (human pial, feline middle cerebral, rabbit, guinea pig and rat basilar arteries). The concentration of CGRP eliciting half-maximal responses ranged from 0.4 nM (human pial artery) to 3 nM (rat and rabbit basilar arteries). Pretreatment of cerebral arteries with low concentrations of either substance P (0.1 nM) or neurokinin A (3 nM) attenuated slightly the CGRP-induced relaxations of guinea pig basilar arteries. Calcitonin was found to be a very weak dilator of cerebral arteries from human and guinea pig. Thus, cardiovascular nerve fibers containing CGRP appear to be present in all mammalian species (although to varying degrees) and CGRP is invariably a potent dilator of the cerebral arteries for all species.

Animals↗

PubMed1987

Immunoreactive delta sleep-inducing peptide in pituitary adrenocorticotropin/alpha-melanotropin cells and adrenal medullary cells of the pig.

Immunoreactive delta sleep-inducing peptide (DSIP) is known to occur in the central nervous system and in body fluids including cerebrospinal fluid, blood and urine. However, the exact nature of the immunoreactive material demonstrated has been a matter of discussion. In the present study, DSIP-like immunoreactivity was demonstrated in the porcine pituitary and adrenal medulla using radioimmunoassay and immunocytochemistry. In the pituitary, the DSIP-like material was present in a subpopulation of the cells storing adrenocorticotropin and alpha-melanotropin. The DSIP immunoreactive cells in the adrenal medulla were identical with a major population of the noradrenaline-storing cells. High-performance liquid chromatography of tissue extracts revealed one major peak of DSIP-like immunoreactivity which did not coelute with synthetic DSIP. The immunoreactive material may represent N-terminally truncated fragments of DSIP. The present results suggest that the anterior and intermediate lobes of the pituitary and the adrenal medulla are potential sources of DSIP-like peptides.

Adrenal Medulla↗

PubMed1987

Motilin response to a glucose load aberrant in smokers.

Smoking is known to influence the blood glucose response to an oral glucose load, possibly by altering the gut motility. Because the peptide hormone motilin might be involved in the regulation of the gastric emptying pattern, we studied 12 heavy smokers and 9 non-smokers after an overnight fast and tobacco abstinence. After an oral glucose load non-smokers showed falling serum motilin levels, as expected, whereas the smokers had initially increasing values. We conclude that smoking affects the gastrointestinal tract, not only during acute nicotine exposure but also chronically.

Blood Glucose↗

PubMed1987

Are gut peptides responsible for the irritable bowel syndrome (IBS)?

Disturbances in gut motor activity have been proposed as a characteristic phenomenon in patients with irritable bowel syndrome (IBS). The symptoms are often associated with food intake. Several neuropeptides have a stimulatory or inhibitory effect on intestinal smooth muscle contraction. Studies on basal and postprandial plasma levels of different neuropeptides have therefore been performed in patients with IBS and been compared with those of a control group. In the whole group of IBS patients no typical gut hormone profile was found in plasma. When the IBS patients were divided into subgroups based on the predominant syndrome changes in the plasma levels of gastrin, motilin and pancreatic polypeptide (PP) were seen. In diarrhoea fasting levels of motilin and PP and postprandial level of PP were increased. In constipated patients fasting levels of gastrin and motilin and postprandial levels of gastrin, motilin and PP were decreased. Fasting and postprandial levels of gastrin were also decreased in patients with predominantly abdominal pain.

Colonic Diseases, Functional↗

PubMed1987

Occurrence and distribution of neuropeptides in the human skin. An immunocytochemical and immunochemical study on normal skin and blister fluid from inflamed skin.

The content and distribution of substance P (SP), somatostatin, vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) in human skin were investigated. Radioimmunoassay was performed on pooled tissue samples from several regions (fingers, toes, axillas and thighs) and on tissue fluid from spontaneous blisters on inflamed skin. Immunocytochemical localization showed all peptides examined except somatostatin to be present in nerve fibers. Nerve fibers storing SP and CGRP, which were found to coexist, were mostly present as free nerve endings in the superficial part of dermis and in epidermis. SP/CGRP fibers were most abundant in fingers and toes. VIP fibers and NPY fibers were localized in the deeper parts of dermis around blood vessels and acini of sweat glands. Also fibers containing these neuropeptides were most common in fingertips and toes. VIP occurred in relatively high amounts also in skin from axilla whereas NPY in this region was below detection limit. Immunoreactive somatostatin was found in low concentrations in tissue extracts and was not present in amounts sufficient for reliable immunostaining. Fluid from spontaneous blisters on inflamed skin contained detectable amounts of all neuropeptides.

Adolescent↗

PubMed1987

Plasma beta-endorphin during clinical and experimental ischaemic pain.

An improved radio-immunoassay using an antiserum directed towards the N-terminal part of the endogenous opioid peptide beta-endorphin 1-31 (beta-EP) was validated and applied to a study of beta-EP in plasma during ischaemic pain. Experimental ischaemic pain induced in seven healthy volunteers by the submaximal effort tourniquet test did not change plasma beta-EP or adrenocorticotrophin. Plasma beta-EP was determined in 21 patients with acute myocardial infarction (AMI) and in seven patients with unstable angina pectoris. Plasma beta-EP was 4.9 fmol/ml with 95% confidence limits, 3.2-7.8 fmol/ml in AMI patients at admittance, and 2.9 (2.0-3.4) fmol/ml one week later in stable and pain-free condition (p less than 0.05). The level in 49 healthy persons was 2.8 (2.4-2.9) fmol/ml. Elevated beta-EP levels were found in five AMI patients with cardiogenic shock and in four AMI patients dying within 24 h after admittance compared to the rest of AMI patients (p less than 0.02). beta-EP was not elevated during unstable angina pectoris, although pain scores were similar to AMI. The AMI group revealed a significant, although weak, positive correlation between plasma beta-EP and pain score (Spearman r = 0.49, p less than 0.05), while there was no correlation during unstable angina pectoris. beta-EP was not correlated to the amount of morphine required within the 48 h after admittance of AMI patients. We conclude that the increase of beta-EP in plasma during AMI may be due to stressful factors other than ischaemic pain and that it is questionable whether beta-EP in plasma is related to antinociception.

Adult↗

PubMed1986

Beta-endorphin-immunoreactive components in human cerebrospinal fluid.

Cerebrospinal fluid (CSF) from patients without neurological disorder was analyzed after Sep-Pak extraction for beta-endorphin (beta-EP)-immunoreactive components by combined reversed-phase high-performance liquid chromatography (HPLC) and radioimmunoassay. A C-terminal directed antibody detected one major immunoreactive component, probably identical with beta-EP1-31. An N-terminal directed antibody detected several immunoreactive components. One co-eluted with beta-EP1-31 but the others are probably C-terminal truncated or otherwise modified forms of beta-EP1-31. However, they eluted differently from beta-EP1-16 (alpha-endorphin), beta-EP1-26, 1-27 and alpha,N-acetyl-beta-EP1-31. Alternatively, some of the fragments may represent C-terminal extended forms of pro-enkephalin A-derived Met-enkephalin. A Met-enkephalin antiserum detected several immunoreactive components probably representing N-terminal extended forms; neither of them were identical with the beta-EP-immunoreactive components. The results illustrate the heterogeneity of the beta-EP-immunoreactive components in CSF and the need to characterize the beta-EP radioimmunoassay before its application to biological extracts.

Aged↗

PubMed1986

Calcitonin gene-related peptide in the eye: release by sensory nerve stimulation and effects associated with neurogenic inflammation.

Calcitonin gene-related peptide (CGRP) in the anterior uvea coexists with tachykinins (substance P and neurokinin A) in sensory nerve fibers deriving from the trigeminal ganglion. Mechanical or electrical stimulation of the intracranial part of the trigeminal nerve/ganglion in rabbits produced a marked hyperemia in the anterior segment of the eye, increased intraocular pressure, breakdown of the blood-aqueous barrier and miosis. Simultaneously, CGRP-like immunoreactivity was released into the aqueous humor. This suggests that the highly vasoactive CGRP can be released from sensory nerve fibers to participate in vascular responses. Unlike the tachykinins, CGRP per se was without effect on the pupillary diameter while disrupting the blood-aqueous barrier (resulting in aqueous flare) upon intravitreal injection. In addition, CGRP enhanced the aqueous flare evoked by a minimal eye trauma (infrared irradiation of the iris). The miosis evoked by the intravitreal injection of substance P was more pronounced when CGRP was injected simultaneously, and finally, substance P induced aqueous flare much more effectively when given together with a threshold dose of CGRP.

Animals↗

PubMed1986

Peptide YY-like immunoreactivity in the central nervous system of the rat.

The concentration of peptide YY (PYY)-like immunoreactivity in rat brain and spinal cord was determined by radioimmunoassay. The highest concentrations were found in the cervical spinal cord (18.1 +/- 1.3 ng/g, mean +/- S.E.M.) and in the medulla oblongata (16.3 +/- 1.5 ng/g). Lower amounts were found in the pons and in the hypothalamus. Chromatographic analysis of the PYY-like immunoreactivity from various regions of the brain revealed 95% of the immunoreactive material to be indistinguishable from synthetic porcine PYY. PYY-immunoreactive nerve cell bodies could be demonstrated by immunocytochemistry in the medulla oblongata of colchicine-treated rats, the largest group of cells being found in the midline area between and partly in the raphe pontis and obscurus nuclei. Another large group of immunoreactive cells was detected more laterally in the medial parts of the gigantocellular reticular nucleus. A few cells, finally, were seen in the dorsal parts of the medulla, including the nucleus of the solitary tract. Varicose nerve fibers displaying PYY immunoreactivity were observed in many parts of the hypothalamus, pons, medulla and spinal cord.

Animals↗

PubMed1986

Localization and effects of neuropeptide Y, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide in human temporal arteries.

Nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) were seen in the adventitia or at the adventitia-media border of the human temporal artery. Pharmacological experiments on isolated temporal artery segments revealed that NPY potentiated the vasoconstrictor responses to noradrenaline, but had no vasoconstrictor ability or only a small vasoconstrictor ability per se. VIP, peptide histidine methionine 27 (PHM-27), SP, neurokinin A (NKA), and CGRP potently relaxed vessels precontracted by prostaglandin F2 alpha, the relative potency being CGRP greater than SP greater than NKA = VIP = PHM-27. The amount of relaxation varied between 67 and 91% of the prostaglandin F2 alpha-induced contraction. The peptide effects were not antagonized by classic adrenergic or cholinergic blockers, suggesting interactions via separate receptor sites.

Calcitonin Gene-Related Peptide↗

PubMed1986

Demonstration of perivascular peptides and changes in concentration with age in man.

By immunocytochemistry, human cerebral arteries have been found to be invested by perivascular fibres which contain neuropeptide Y, substance P and vasoactive intestinal polypeptide (VIP). The concentrations of the peptides are comparable for substance P and VIP, whereas that of neuropeptide Y is much higher. A marked reduction in radioimmunoassayable peptide levels was observed with advancing age of the patients.

Adolescent↗

PubMed1986

Calcitonin gene-related peptide in thyroid nerve fibers and C cells: effects on thyroid hormone secretion and response to hypercalcemia.

Calcitonin gene-related peptide (CGRP) in the thyroid has a dual localization to nerve fibers around blood vessels and follicles and to parafollicular (C) cells. CGRP was found to coexist with substance P (SP) in most of the nerve fibers; a few CGRP fibers seemed to lack SP, and a few SP fibers seemed to be devoid of CGRP. In the C cells, CGRP coexisted with calcitonin (CT). Cervical vagotomy (extirpation of the nodose ganglion) eliminated approximately 50% of the CGRP/SP fibers in the thyroid without any overt influence on CGRP/CT in the C cells. Removal of the superior cervical ganglion or chemical sympathectomy (6-hydroxydopamine treatment) affected neither thyroid CGRP/SP nerve fibers nor CGRP/CT-storing C cells. CGRP nerve cell bodies were numerous in the jugular-nodose ganglionic complex (notably in the jugular portion); in many of them, CGRP coexisted with SP. A few scattered CGRP nerve cell bodies also occurred in the laryngeal ganglion, whereas none was found in the thyroid ganglion. Hypercalcemia evoked by vitamin D2 treatment, which is known to degranulate thyroid C cells, reduced the thyroid content of both CGRP and CT. As tested in mice in vivo, CGRP and SP alone or together had no effect on basal or TSH- or isoprenaline-induced thyroid hormone secretion. Vasoactive intestinal peptide-stimulated iodothyronine release, on the other hand, was enhanced by CGRP, but not by SP. SP had no effect on combined vasoactive intestinal peptide-CGRP-stimulated iodothyronine release. These findings suggest that CGRP participates in the control of thyroid hormone secretion and that, like CT, CGRP in the C cells is under control of the serum calcium level.

Animals↗

PubMed1986

Motilin in chronic idiopathic constipation.

The plasma motilin levels were studied in seven patients with severe long-standing idiopathic constipation before and after a fat-rich test meal. The results were compared with those of a control group consisting of 10 apparently healthy persons with normal bowel function. The constipated patients had reduced basal motilin levels and a reduced motilin release after the test meal. Motilin is known to stimulate intestinal motility by inducing interdigestive descending contractions in the stomach and small intestine. A defective motilin release may therefore play a part in the pathogenesis of idiopathic constipation.

Adult↗

PubMed1986

Substance P and vasoactive intestinal peptide in bullous and inflammatory skin disease.

Immunoreactivity (IR) of substance P (SP) and Vasoactive Intestinal Peptide (VIP) were determined by radioimmunoassay in serum of 56 patients with inflammatory skin diseases, in blister fluid of 40 patients with spontaneous blisters and 31 subjects with induced skin blisters. Serum concentrations of SP-IR and VIP-IR were mostly low or non-detectable. Spontaneous blisters contained high amounts of SP-IR, particularly in bullous pemphigoid and in some inflammatory dermatoses, while VIP-IR levels usually were low. Suction blisters from inflamed but not from normal skin often contained SP-IR but more seldom VIP-IR.

Adolescent↗

PubMed1985

Innervation of the feline cerebral vasculature by nerve fibers containing calcitonin gene-related peptide: trigeminal origin and co-existence with substance P.

The presence of a population of nerve fibers containing immunoreactive calcitonin gene-related peptide (CGRP) has been demonstrated around cerebral arteries of the cat with immunocytochemistry and radioimmunoassay. CGRP immunoreactivity in the feline cerebral vasculature, as characterized by high-performance liquid chromatography, is similar to authentic rat CGRP. Numerous perikarya containing CGRP are present in the trigeminal ganglia, and surgical lesions of the trigeminal ganglia significantly reduce the levels of CGRP in the cerebral vasculature, suggesting that this cranial nerve is the principal origin of these cerebrovascular nerve fibers. As demonstrated by sequential immunocytochemistry, CGRP coexists with substance P both in the trigeminal ganglion and nerve fibers around cerebral blood vessels. The presence of CGRP in the cerebrovascular trigeminal innervation provides further versatility and complexity for this sensory afferent system putatively involved in the transmission of intracranial pain.

Animals↗

PubMed1985

Bombesin, neurotensin and pro-gamma-melanotropin immunoreactants in human milk.

The concentration of bombesin-like, neurotensin-like and pro-gamma-melanotropin-like immunoreactants in human skim milk was measured by radioimmunoassay and found to be 235 pg/ml (mean, n = 13, range 60-430 pg/ml), 63 pg/ml (mean, n = 13, range 20-105 pg/ml) and 2.4 ng/ml (mean, n = 6, range 1.2-5 ng/ml), respectively. The concentrations were 5-10 times higher than in plasma. High performance liquid chromatography showed that the neurotensin and pro-gamma-melanotropin immunoreactants co-eluted with the authentic peptides. Bombesin gave three peaks, one co-eluting with authentic bombesin and one with porcine gastrin releasing peptide 14-27, whereas another one had a shorter elution time, suggesting a less hydrophobic fragment, possibly even smaller than gastrin releasing peptide 14-27.

Bombesin↗

PubMed1985

Regulatory peptides in the lower esophageal sphincter of man.

Smooth muscle specimens were taken from the lower esophageal sphincter of patients suffering from achalasia or hiatus hernia with gastro-esophageal reflux. The specimens were analysed for neurohormonal peptides using immunochemistry and immunocytochemistry. Control specimens were obtained from patients subjected to esophageal resection because of esophageal cancer. The concentration of vasoactive intestinal polypeptide (VIP) was higher and the VIP nerve supply greater in patients with hiatus hernia than in control patients. The VIP nerve supply and the content of this peptide was lower in patients with achalasia than in controls. The same tendency was observed for substance P and enkephalin although the changes in their concentrations were not statistically significant. Enkephalin fibers were few, both in specimens from control patients and from patients with hiatus hernia; they could not be detected in specimens from patients with achalasia. Never fibers containing somatostatin or gastrin/cholecystokinin could not be detected in any of the groups and somatostatin and gastrin/cholecystokinin could not be measured in extracts of the lower esophageal sphincter. We propose that changes in the concentration of neuropeptides may at least contribute to manifestations of achalasia and of decreased lower esophageal sphincter pressure and gastro-esophageal reflux.

Adolescent↗