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Biomedical subjects

R Uddman

Publications and source records attributed to R Uddman.

At least 127 records · Page 7Linked to original sources

Occurrence and distribution of calcitonin gene-related peptide in the mammalian respiratory tract and middle ear.

Nerve fibres displaying immunoreactivity to calcitonin gene-related peptide (CGRP) are abundantly distributed in the respiratory tract of man, dog, cat, guinea-pig, rat and mouse. Numerous fine, beaded CGRP fibres were seen in the middle ear mucosa, and a moderate supply was found in the ear drum. In the nasal mucosa and in the wall of the Eustachian tube CGRP fibres occurred around blood vessels, arteries in particular. A conspicuously rich supply of CGRP fibres was seen beneath and within the epithelium. In addition, a few fibres were seen in smooth muscle bundles and close to sero-mucous glands. In the tracheo-bronchial wall CGRP fibres were distributed beneath and within the epithelium, in vascular and non-vascular smooth muscle and sometimes close to small glands. A few CGRP-immunoreactive endocrine-like cells were, in addition, distributed in the tracheal epithelium of cat, rat and mouse. The trigeminal, spinal and nodose ganglia, studied in rats and guinea-pigs, harboured numerous CGRP-immunoreactive nerve cell bodies. The cervical sympathetic ganglia were devoid of immunoreactive neuronal perikarya. Surgical and chemical (6-hydroxydopamine treatment) sympathectomy did not affect the number and distribution of CGRP fibres. The distribution of CGRP fibres in the respiratory tract suggests that CGRP may take part in sensory transmission. In addition, CGRP may affect the regulation of local blood flow, smooth muscle tone and glandular secretion.

Animals↗

Nerve fibres containing peptide histidine isoleucine (PHI) in the respiratory tract.

Recent studies have indicated that vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are formed by cleavage of a common precursor protein. In the present study we have examined the distribution of nerve fibres displaying PHI-like immunoreactivity in the upper respiratory tract of several mammalian species including man. PHI fibres were found to have the same general distribution as previously described for VIP fibres. These fibres were distributed mainly in the subepithelial connective tissue around both seromucous glands and blood vessels. In the tracheal wall, PHI fibres were also seen in the non-vascular smooth muscle. Sequential immunostaining for PHI and VIP revealed co-existence of the two peptides in the same nerve fibres.

Animals↗

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↗

Neuropeptide Y-like immunoreactivity in perivascular nerve fibres of the guinea-pig.

The distribution of perivascular nerve fibres displaying neuropeptide Y-like immunoreactivity was studied in the guinea-pig. Generally, neuropeptide Y fibres were numerous around arteries and moderate in number around veins. In the heart, immunoreactive fibres were numerous in the auricles and the atria (epi- and endocardium) whereas the ventricles had a more scarce supply. The coronary vessels were richly supplied with fibres. Around large elastic and muscular arteries the fibres formed well developed plexuses. Small arteries in the respiratory tract, the gastrointestinal tract and the genito-urinary tract received a particularly rich supply. In the liver, spleen and kidney only few perivascular fibres were seen. Since immunoreactive fibres around blood vessels disappeared upon surgical or chemical sympathectomy, and sequential immunostaining with antisera against dopamine-beta-hydroxylase (a marker for adrenergic neurons) and against neuropeptide Y revealed their co-existence, it is concluded that neuropeptide Y fibres around blood vessels are sympathetic and adrenergic.

Animals↗

Innervation of human omental arteries and veins and vasomotor response to noradrenaline, neuropeptide Y, substance P and vasoactive intestinal peptide.

Human omental arteries and veins are supplied with nerve fibers containing noradrenaline (NA) and neuropeptide Y (NPY); these two agents probably co-exist in perivascular sympathetic nerve fibers. Substance P (SP)- or vasoactive intestinal peptide (VIP)-containing fibers could not be detected. In studies on isolated omental vessels NA produced constriction. The results of blockade experiments suggest that human omental arteries are equipped predominantly with alpha 1-adrenoceptors and omental veins with a mixture of alpha 1- and alpha 2-adrenoceptors. NPY at a concentration of 10(-7) M or higher had a weak contractile effect on veins and virtually no effect on arteries. NPY at a concentration of 3 X 10(-8) M shifted the NA concentration response curve to the left in arteries (pD2 = 5.8 for NA versus 6.6. for NA in the presence of NPY; P less than 0.001) but not in veins. Both SP and VIP relaxed arteries precontracted with NA or prostaglandin F2 alpha (PGF2 alpha). The potency of SP as a relaxant agent was similar in arteries and veins; the effect of VIP was elicited at lower concentrations in veins than in arteries.

Aged↗

Occurrence and distribution of neuropeptide-Y-immunoreactive nerves in the respiratory tract and middle ear.

Nerve fibres displaying neuropeptide-Y (NPY) immunoreactivity are abundantly distributed in the respiratory tract of cats, guinea-pigs, rats and mice. Fine beaded NPY fibres were seen in whole-mount spreads of the middle-ear mucosa. In the nasal mucosa and in the wall of the Eustachian tube NPY fibres were numerous around arteries and arterioles but sparse in the vicinity of veins; single fibres were found close to the acini of seromucous glands. In the tracheobronchial wall NPY fibres occurred in the proximity of blood vessels, in the subepithelial layer and in the smooth muscle. Surgical and chemical (6-hydroxydopamine treatment) sympathectomy resulted in disappearance of adrenergic and NPY-containing nerve fibres in the nasal mucosa. Sequential staining with antibodies against dopamine-beta-hydroxylase (DBH) and NPY revealed that DBH and NPY occur in the same perivascular nerve fibres in the nasal mucosa. The distribution of NPY fibres in the respiratory tract suggests multiple functions of NPY, such as regulation of local blood flow, glandular secretion and smooth muscle activity.

Adrenergic Fibers↗

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↗

Occurrence and distribution of GRP-immunoreactive nerve fibres in the respiratory tract.

The occurrence and distribution of nerve fibres containing gastrin-releasing peptide (GRP) were investigated in the respiratory tract of several mammals using immunocytochemistry. A moderate supply of nerve fibres displaying GRP immunoreactivity was seen in the middle ear mucosa, the nasal mucosa and the tracheobronchial wall. Generally, the fibres were distributed around blood vessels and seromucous glands. In addition, scattered GRP fibres were seen in the smooth muscle of the tracheal wall. The distribution of GRP fibres in the respiratory tract suggests multiple functions of GRP such as regulation of local blood flow, glandular secretion and smooth muscle activity.

Animals↗

Neuropeptide Y co-exists and co-operates with noradrenaline in perivascular nerve fibers.

Neuropeptide Y (NPY)-immunoreactive nerve fibers were numerous around arteries and few around veins. NPY probably co-exists with noradrenaline in such fibers since chemical or surgical sympathectomy eliminated both NPY and noradrenaline from perivascular nerve fibers and since double staining demonstrated dopamine-beta-hydroxylase, the enzyme that catalyzes the conversion of dopamine to noradrenaline, and NPY in the same perivascular nerve fibers. Studies on isolated blood vessels indicated that NPY is not a particularly potent contractile agent in vitro. NPY greatly enhanced the adrenergically mediate contractile response to electrical stimulation and to application of adrenaline, noradrenaline or histamine, as studied in the isolated rabbit gastro-epiploic and femoral arteries. The potentiating effect of NPY on the response to electrical stimulation is probably not presynaptic since NPY affected neither the spontaneous nor the electrically evoked release of [3H]noradrenaline from perivascular sympathetic nerve fibers.

Animals↗

Indoleaminergic mechanisms in brain vessels; localization, concentration, uptake and in vitro responses of 5-hydroxytryptamine.

Immunocytochemical studies have revealed the presence of 5-HT-containing nerve fibres in all parts of the cerebrovascular bed (arteries, arterioles and veins) of mouse, rat, guinea-pig, rabbit and cat. Biochemical measurements (using HPLC) revealed substantial concentrations of 5-HT and 5-HIAA in the pial vessels of the rat, rabbit, cat and man, the amounts corresponding well with the density of the perivascular nerve supply. The uptake of 3H-5-HT was studied in arteries removed from the circle of Willis in rats. Maximum uptake was reached after 15 min of incubation at 37 degrees C and plateaued at 30 min. The reaction was temperature-dependent and found to be absent if performed at 0 degrees C. Pharmacological experiments on isolated middle cerebral and basilar arteries showed that vessels from rat and dog were contracted by approximately 90% upon administration of 5-HT, whereas vessels from guinea-pig, rabbit, cat and man were contracted by 40 to 60% relative to 124 mM K+. The EC50 values in the different species varied by between 1.5 X 10(-7) M (rat) and 3 X 10(-9) M (dog). The 5-HT-induced contractions were blocked by the 5-HT antagonists, methysergide, methergoline and ketanserin. Transmural nerve stimulation (TNS) of the rabbit basilar artery revealed a tetrodotoxin sensitive constriction whereas TNS of cat and dog middle cerebral arteries caused a tetrodotoxin-sensitive relaxation. The relaxation was not significantly attenuated until high doses of methergoline (3 X 10(-6) M) or ketanserin (3 X 10(-5) M) had been given.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neuropeptide Y: immunocytochemical localization to and effect upon feline pial arteries and veins in vitro and in situ.

Plexuses of nerve fibres containing neuropeptide Y (NPY)-like immunoreactivity invest pial arteries belonging to the circle of Willis, pial arterioles, occasionally penetrating arterioles and large veins. A more sparse supply of NPY-like fibres were observed around pial veins and venules. The NPY-immunoreactive fibres are located within the adventitia or at the adventitia-media border. Only occasional fibres are present in cerebral vessels of animals in which the superior cervical ganglion has been removed one week previously. Administration of NPY resulted in strong, concentration-dependent contractions of isolated feline middle cerebral arteries whereas administration of avian pancreatic polypeptide (APP) elicited weak contractions. In chloraloseanaesthetized cats, perivascular microapplication of NPY in situ resulted in marked concentration-dependent contractions of cerebral pial arterioles (34.7 +/- 6.6%; maximum decrease in calibre with NPY. Perivascular administration of NPY resulted in the constriction of pial veins but the magnitude of the venous calibre reductions was smaller than the response of arterioles at each reductions was smaller than the response of arterioles at each concentration examined. APP did not elicit contraction of pial arterioles or veins during in situ conditions. The pharmacological and immunocytochemical results strongly indicate the existence of a novel perivascular neuronal system containing NPY, which mediates contraction of cerebral blood vessels and NPY is colocalized with NA in sympathetic nerves.

Animals↗

Neuropeptide Y in the thyroid gland: neuronal localization and enhancement of stimulated thyroid hormone secretion.

Nerve fibers displaying neuropeptide Y (NPY) immunoreactivity occurred around blood vessels and follicles in the thyroid gland of several mammals, including man. Removal of the superior cervical ganglia or chemical sympathectomy (6-hydroxydopamine treatment) markedly reduced the number of NPY-containing nerve fibers in the thyroid and eliminated norepinephrine-containing fibers. NPY-immunoreactive nerve cell bodies were numerous in the superior cervical ganglia of mouse, rat, and guinea pig. Not unexpectedly, therefore, immunocytochemistry involving sequential staining with antibodies against dopamine-beta-hydroxylase (an enzyme marker for adrenergic neurons) and NPY revealed that most of the NPY fibers were adrenergic. As tested in mice in vivo, NPY did not affect basal or norepinephrine-stimulated thyroid hormone secretion, but enhanced isoprenaline-, TSH-, and vasoactive intestinal polypeptide-induced iodothyronine release. These findings suggest a modulatory role for NPY in the control of thyroid hormone secretion.

Animals↗

Neuropeptide Y: occurrence and distribution in dental pulps.

Nerve fibers displaying neuropeptide Y (NPY) immunoreactivity were seen in the dental pulp of several mammals, including man. Generally, the NPY fibers were more numerous in the apical part than in the coronal part and were distributed around small blood vessels and as single fibers in the pulpal stroma. Sequential staining with antibodies against the enzyme dopamine-beta-hydroxylase (DBH), a marker for adrenergic neurons, and NPY showed that DBH and NPY were located in the same perivascular nerve fibers. Further, since chemical and surgical sympathectomy caused the disappearance of pulpal NPY fibers, it is conceivable that NPY fibers in the dental pulp are identical with adrenergic ones. There is thus a morphological basis for suggesting that NPY and noradrenaline cooperate in regulating pulpal blood flow.

Adrenergic Fibers↗

Neuropeptide Y immunoreactive neurons in the guinea-pig uvea and retina.

Neuropeptide Y (NPY) is a recently discovered, amidated 36 amino acid residue neuropeptide present in many but not all sympathetic noradrenergic neurons. In the guinea-pig eye, NPY immunoreactive fibers were found to have the same distribution as noradrenergic fibers except that there were fewer at the iris dilator, in the cornea, and in the chamber angle. In the anterior uvea, the NPY immunoreactive fibers disappeared after excision of the homolateral superior cervical sympathetic ganglion, whereas in the choroid, many NPY immunoreactive fibers remained, indicating that they originate elsewhere. NPY immunoreactivity thus is not found in all sympathetic adrenergic neurons nor is it found only in such nerve fibers. In the retina, NPY immunoreactive fibers formed a single layer of processes in sublamina 1 of the inner plexiform layer. NPY immunoreactive cell bodies were found in the innermost cell row of the inner nuclear layer. The immunoreactivity was concentrated to the hillock region of these cells.

Adrenergic Fibers↗

Neuropeptide Y: cerebrovascular innervation and vasomotor effects in the cat.

Avian pancreatic polypeptide (APP) has been proposed to be a neurotransmitter in a subpopulation of sympathetic nerves. Here, we present immunocytochemical and pharmacological evidence that the structurally related peptide, neuropeptide Y (NPY), is likely to be the biologically active material in these nerves. Cerebral arteries from cats are invested with a dense network of NPY-containing nerve fibres, as demonstrated by immunocytochemistry. This immunoreaction is abolished by prior removal of the superior cervical ganglion. NPY causes strong contractions of cerebral arteries in vitro whereas APP has small effects on the vasomotor reactivity. The NPY-induced contractions were not inhibited by the alpha 2-adrenoceptor antagonist rauwolscine (10(-7) M) or the 5-hydroxytryptamine antagonist ketanserin (10(-7) M). The contractions were, however, sensitive to calcium removal or to the calcium antagonist diltiazem (10(-4) M).

Animals↗

Substance P: localization, concentration and release in cerebral arteries, choroid plexus and dura mater.

Substance P-like immunoreactivity (SPLI) was studied by immunocytochemistry and radioimmunoassay in the cerebral arteries, choroid plexus and dura mater of the guinea-pig, rabbit, cat and man. The highest concentrations were found in cerebral blood vessels: 6.1 +/- 2.3 pmol/g (guinea-pig), 9.0 +/- 1.1 pmol/g (rabbit), 7.1 +/- 0.4 pmol/g (cat), and 2.4 +/- 0.9 pmol/g (man). Lower levels were obtained in the choroid plexus and dura mater. The distribution of substance P (SP)-immunoreactive nerve fibres found in various regions of the guinea-pig correlated well with the amount of SPLI measured. Sympathectomy did not alter the concentration of SPLI in the dura mater or in cerebral blood vessels. Electrical field stimulation or 124 mM potassium enhanced the spontaneous efflux of SPLI by 10 and 20%, respectively, from superfused pial arteries in vitro. These data are in support of a functional role of perivascular SP within the cranial circulation.

Animals↗

Substance-P-containing nerve fibers in the nasal mucosa.

Nerve fibers displaying SP immunoreactivity were detected in the nasal mucosa of several mammals. The fibers were seen around small blood vessels, seromucous glands, and beneath and sometimes within the surface epithelium. In the pterygopalatine ganglion and the trigeminal ganglion, known to innervate the nasal mucosa, SP-positive nerve cell bodies were seen. Sympathetic denervation with 6-hydroxydopamine (6-OHDA) or bilateral cervical sympathectomy did not visibly affect the distribution of SP fibers in the nasal mucosa in mice or rats. The findings are compatible with the view that the bulk of SP fibers to the nasal mucosa derive from the trigeminal ganglion with a possible contribution from the pterygopalatine ganglion.

Acetylcholinesterase↗

Immunohistochemical localization of substance P, vasoactive intestinal polypeptide and gastrin-releasing peptide in vas deferens and seminal vesicle, and the effect of these and eight other neuropeptides on resting tension and neurally evoked contractile activity.

Immunohistochemical studies of the vas deferens and seminal vesicle of mouse, guinea-pig, and rabbit showed the presence of nerve fibres containing vasoactive intestinal polypeptide (VIP), substance P (SP), and gastrin-releasing peptide (GRP) supplying the smooth muscle layers as well as blood vessels. The nerve supply was better developed in the seminal vesicle than in the vas deferens. The motor activity of the vas deferens and seminal vesicle of the guinea-pig was studied in vitro. The vas deferens responded to transmural electrical stimulation with a twitch followed by a slow contraction. The twitch was blocked by guanethidine and tetrodotoxin, but not by atropine, propranolol, phenoxybenzamine, or fluphenazine. The slow contraction exhibited features of an alpha-receptor-mediated response. SP, physalaemin and eledoisin contracted the smooth muscle and also potentiated the twitch response to electrical nerve stimulation in a concentration-dependent manner. The SP blocking agent, (D-Pro2,D-Trp7,9)-SP, affected neither the resting tension nor the response to electrical stimulation. It is therefore suggested that the SP fibres act mainly prejunctionally. VIP, Leu-enkephalin, cholecystokinin octapeptide (CCK-8), angiotensin II, vasopressin, neurotensin, bombesin, and GRP had no effect on either the resting tension or the response to electrical nerve stimulation. The seminal vesicle responded to electrical stimulation with a contraction which was unimpaired by atropine, propranolol, phenoxybenzamine, and guanethidine, but abolished by tetrodotoxin. Hence, this contraction is mediated by a non-adrenergic, non-cholinergic neurotransmitter. Bombesin, GRP, SP, physalaemin and eledoisin contracted the smooth muscle and potentiated the response to electrical stimulation. VIP, Leu-enkephalin, CCK-8, angiotensin II, vasopressin, and neurotensin had no effect on the resting tension or on the response to transmural electrical stimulation. The SP antagonist abolished the contraction elicited by SP but did not influence the response to nerve stimulation. The results suggest that the SP and GRP nerves may have prejunctional and facilitating postjunctional effects in the seminal vesicle.

Animals↗