Neuropeptide Y-containing Nerve Fibers Research Articles

Neuropeptide Y in the adult and fetal human pineal gland.

Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

Neuropeptide Y (NPY) in the orbital arteries of the rabbit. Immunocytochemistry and vasomotor activity.

The purpose of the present study was to investigate the presence and vascular effects of neuropeptide Y in the rabbit orbital arteries. Neuropeptide Y-containing nerve fibers were demonstrated, using an indirect immunofluorescence method with a neuropeptide Y antiserum raised in goat against porcine neuropeptide Y. Isometric responses in isolated circular segments of the orbital arteries were measured following application of neuropeptide Y, different contracting agonists, and the neuropeptide Y blocker alpha-trinositol. A rich supply of neuropeptide Y-containing nerve fibers was seen around the orbital arteries. Neuropeptide Y (10(-10)-10(-6) M) did not induce any contractions in resting arterial segments. Noradrenaline and histamine evoked concentration dependent constrictions which were potentiated by neuropeptide Y (3 x 10(-7) M). This potentiation was completely blocked by alpha-trinositol (3 x 10(7) M). The contractile effects of endothelin-1, endothelin-3, prostaglandin F2 alpha, and 5-hydroxytryptamine were not modified by neuropeptide Y.

The action of palytoxin on the isolated detrusor muscle of the rat.

1. The effects of a coelenterate toxin, palytoxin (PTX) have been studied in the isolated detrusor muscle. of the rat. 2. PTX (1-100 nM) initiated concentration-dependent contractions of the detrusor; the contraction led to an irreversible tachyphylaxis. Muscle desensitized to PTX continued to respond to acetylcholine (ACh) and excess K+ but the contractions were reduced compared to pre-PTX contractions. 3. Contractions evoked by PTX were not affected by the presence of atropine (10 microM), indomethacin (10 microM) or tetrodotoxin (0.5 microM) but were greatly reduced by nifedipine (3 microM) and by the absence of K+. PTX could not evoke contractions in the absence of Ca2+ or in tissues depolarized by exposure to excess K+. 4. PTX abolished the neurogenic contractile responses to electrical field stimulation (EFS). 5. Combined treatment with atropine (10 microM) plus nifedipine (3 microM) abolished contractile responses to EFS and greatly reduced the contractile response to PTX. 6. The contractile response to PTX (100 nM) was reduced following exposure of the muscle to alpha, beta-methylene ATP. 7. Exposure to PTX (100 nM) for 1-3 h reduced both the ACh content of the detrusor (by more than 80%), and the immunoreactivity of neuropeptide Y-containing nerve fibres compared to control. 8. It is concluded that the primary effect of PTX is to promote the release of endogenous motor transmitters, leading to their eventual depletion.

Light and electron microscopy of neuropeptide Y-containing nerves in human liver, gallbladder, and pancreas

Neuropeptide Y-containing nerve fibers were identified by light and electron microscopic immunocytochemistry in the human liver, gallbladder, and pancreas. In the liver, neuropeptide Y-containing nerve fibers were distributed richly in Glisson's sheath and were prominent around the walls of the interlobular vein, interlobular hepatic artery, and hepatic bile duct. The fibers also formed a dense network surrounding the hepatocytes. The nerve terminals were found close to the endothelial cells of blood vessels, as well as being distributed in Disse's space, where they appeared to terminate. Occasionally these terminals contacted directly the membrane of a hepatocyte. In the gallbladder, neuropeptide Y fibers were found in each layer, with an especially dense network in the lamina propria. The fibers also ran close to the epithelium and parallel to the muscle bundles. Blood vessels throughout the gallbladder were well supplied with such nerve fibers. In the pancreas, neuropeptide Y fibers were found mainly near blood vessels and partly in gaps between exocrine glands, seeming to terminate on certain endocrine cells. Nerve terminals were located in the vascular walls and adjacent to the surface of exocrine acinar cells. These studies provide a basis for correlating the neuropeptide Y distribution with pharmacological and physiological studies in humans.

Neuropeptide Y immunoreactivity in the mammalian liver: pattern of innervation and coexistence with tyrosine hydroxylase immunoreactivity

The distribution of nerve fibers displaying neuropeptide Y immunoreactivity in relationship to the catecholaminergic innervation of rat, guinea pig, and rabbit liver was investigated by single- and double-label immunofluorescence methods. In all three species, neuropeptide Y-immunoreactive fibers are prominent in association with the vasculature, biliary pathway, and stromal compartment. The neuropeptide Y innervation of the parenchyma, on the other hand, differs among the three species in term of density. It is quite sparse in the rat and rabbit, particularly in the former species. In the guinea pig liver, numerous single, varicose neuropeptide Y-containing nerve fibers innervate the hepatic parenchyma; often, thin processes surround single hepatocytes and lie close to sinusoids. The immunoreactive pattern of tyrosine hydroxylase, a marker for catecholaminergic neurons and fibers, is comparable to that of neuropeptide Y. Most neuropeptide Y-containing nerve fibers also contain tyrosine hydroxylase immunoreactivity, in all three species, with the exception of the rabbit parenchyma, where a substantial proportion of catecholaminergic fibers lack immunoreactivity for neuropeptide Y. Finally, systemic administration of the sympathetic neurotoxin, 6-hydroxydopamine, in rats and guinea pigs resulted in virtually complete elimination of both neuropeptide Y- and tyrosine hydroxylase-immunoreactive fibers. These findings are consistent with the hypothesis that neuropeptide Y-containing nerve fibers form a subpopulation of the sympathetic innervation of the mammalian liver, which is likely to originate from prevertebral sympathetic ganglia.

Perivascular Innervation of the Cerebral Arteries in Spontaneously Hypertensive Rats—An Immunohistochemical Study

Perivascular innervation in cerebral arteries of spontaneously hypertensive rats and of normotensive Wistar-Kyoto rats was studied. Adrenergic nerve fibers and neuropeptide Y-containing nerve fibers, indicative of vasoconstrictor nerves, were denser in all cerebral arteries of spontaneously hypertensive rats than those of Wistar-Kyoto rats. In contrast, cholinergic nerve fibers and vasoactive intestinal polypeptide, substance P-containing nerve fibers, indicative of vasodilator nerves, remained unchanged in all cerebral arteries of spontaneously hypertensive rats, as compared with findings in the Wistar-Kyoto rats. Thus, not only adrenergic nerve fibers but also neuropeptide Y-containing nerve fibers may play an important role in preventing the disruption of the blood-brain barrier and the development of hypertensive encephalopathy in spontaneously hypertensive rats.

Distribution of somatostatin- and neuropeptide Y-immunoreactive nerve fibers in the porcine female reproductive system

The localization and distribution of somatostatin and neuropeptide Y were studied in the porcine female reproductive system with the indirect immunofluorescence technique. Somatostatin-immunoreactive nerve fibers were observed in different parts of the ovary and in the muscular membrane of the uterus as well as in the mesosalphinx. Somatostatin-immunoreactive neurons were detected in the inferior mesenteric ganglion. Neuropeptide Y immunoreactivity was present in a large number of nerve fibers distributed in different regions of the uterus, oviduct and ovary. The present results suggest that the porcine female genital organs receive innervation by somatostatin- and neuropeptide Y-containing nerve fibers, but their exact functional role remains to be established.

Neuropeptide Y in non-sympathetic nerves of the rat: Changes during maturation but not after guanethidine sympathectomy

Non-sympathetic neuropeptide Y-containing nerves were demonstrated by their persistence after destruction of sympathetic nerve terminals by acute 6-hydroxydopamine treatment for 48 h. In order to examine whether these neuropeptide Y-containing nerves reinnervate tissues following the loss of sympathetic nerves we administered guanethidine sulphate to one-week-old rat pups for three weeks to produce a complete and long-lasting sympathectomy and we monitored the innervation of the superior cervical ganglion, mesenteric vein, vas deferens and urinary bladder by noradrenaline- and neuropeptide Y-containing nerves two and 16 weeks later (assay and histochemical observations). By two weeks the reduction in neuropeptide Y content of tissues was similar to the reduction after acute sympathectomy with 6-hydroxydopamine treatment, indicating that there was no early reinnervation by non-sympathetic neuropeptide Y-containing nerve fibres at a time when sensory transmitters increase. Furthermore, there was no reinnervation by neuropeptide Y-containing nerve fibres by the time these sympathectomized animals had reached maturity, 16 weeks after cessation of treatment. Neuropeptide Y levels increased in the superior cervical ganglion with normal maturation but decreased in the prostatic end of the vas deferens. A non-sympathetic source of neuropeptide Y demonstrated in the immature rat vas deferens was no longer evident in the mature animal.

Immunohistochemical study of neuropeptide Y-containing nerve fibers in the human clitoris and penis

The occurrence and distribution of neuropeptide Y in the human clitoris and penis was investigated by light immunohistochemistry. Neuropeptide Y-containing nerve fibers were detected in the tunicae of arteries and veins as well as among trabecular smooth muscle. The distribution pattern of the peptide was similar in both organs although a higher density of immunoreactive nerve fibers was detected in the penis. The immunolocalization of neuropeptide Y was also compared with that of neuron-specific enolase, a neuronal marker which labels the entire nerve network. It is suggested that neuropeptide Y is involved in the physiology of the penis and the clitoris, affecting vascular and nonvascular smooth muscle activity.

Pregnancy reduces noradrenaline but not neuropeptide levels in the uterine artery of the guinea-pig

Using histochemical, immunohistochemical and biochemical techniques, noradrenaline-, neuropeptide Y-, vasoactive intestinal polypeptide-, substance P- and calcitonin gene-related peptide-containing nerve fibres were studied in the uterine artery of virgin, progesterone-treated and pregnant guinea-pigs. Morphological changes following hormone treatment or in pregnancy were also evaluated in a quantitative study on semithin sections of the uterine artery. In late pregnancy, the number of noradrenaline-containing nerve fibres, which formed the densest plexus in virgin animals, was significantly decreased, a finding supported by a significant reduction in noradrenaline levels. This reduction was not mimicked by systemic progesterone treatment. In contrast, the innervation of the uterine artery by neuropeptide Y-containing nerve fibres was increased in pregnancy, while the other peptidergic nerves and peptide levels were unchanged after progesterone treatment and in pregnancy. These changes led to a predominance of innervation by neuropeptide Y- rather than noradrenaline-containing nerve fibres in late pregnancy. No morphological changes were detected following progesterone treatment, but pregnancy led to a marked increase in the cross-sectional area of the vessel accompanied by an increase in the thickness of the media.

Peptide-containing neurons projecting to the vocal cords of the rat: retrograde tracing and immunocytochemistry

The distribution and origin of neuropeptide Y-, vasoactive intestinal peptide- and calcitonin gene-related peptide-containing nerve fibers and adrenergic (dopamine-β-hydroxylase-containing) fibers in the rat larynx were studied by retrograde tracing and selective denervations in combination with immunocytochemistry. An injection of the retrograde tracer True Blue to the right vocal cord resulted in the appearance of labelled nerve cell bodies in the ipsi- and contralateral superior cervical and stellate ganglia, the thyroid ganglia, the jugular-nodose ganglionic complexes, in the ipsilateral trigeminal and dorsal root ganglia at levels C 2 and C 3 and in local tracheal ganglia. Judging from the number of labelled nerve cell bodies, the jugular-nodose ganglionic complexes, dorsal root ganglia and superior cervical ganglia provide the greater part of the vocal cord innervation. Most of the True Blue-labelled nerve cell bodies in the superior cervical and stellate ganglia contained neuropeptide Y. In the thyroid ganglia the majority of labelled nerve cell bodies contained vasoactive intestinal peptide. In the jugular-nodose ganglionic complex and the dorsal root ganglia the majority of the labelled nerve cell bodies stored calcitonin gene-related peptide. Retrograde tracing and denervation studies revealed that all noradrenaline- and the majority of neuropeptide Y-containing nerve fibers emanate from the superior cervical and stellate ganglia. A minor population of neuropeptide Y-containing nerve fibers originate in local tracheal ganglia. The vasoactive intestinal peptide-containing nerve fibers originate in the thyroid ganglion and local tracheal ganglia, whereas calcitonin gene-related peptide-containing nerve fibers emanate from the dorsal root ganglia (C 2C 3), the trigeminal ganglia and the jugular-nodose ganglia.

Neuropeptide Y reduces ovarian blood flow in the rabbit

Neuropeptide Y-containing nerve fibers have previously been demonstrated to innervate the mammalian ovary. These nerve fibers innervate primarily the vasculature. In this study we have developed a method for in vivo measurement of the ovary blood flow rate by means of the 133Xe method. Using this technique we measured the ovary blood flow rate and investigated the dose-response relationship between close intraarterial-injected NPY and the ovary blood flow rate. A monoexponential washout curve for 133Xe was found for the whole washout process, ensuring that the blood flow rate at any time could be calculated from the curve. We found a mean blood flow rate in the nonpregnant rabbit ovary at 43.6±4.4 ml·(100 g) −1· min −1 (mean±SEM). Injection of NPY (20, 200, 2000 pM) in the aorta close to a. ovarica resulted in a dose-dependent decrease in the ovarian blood flow rate with a maximum reduction to 40.7±6.3% (mean±SEM) of the control blood flow rate. These findings make it likely that receptors able to interact with NPY are present in the vasculature of the rabbit ovary.

Neuropeptide Y Co-Exists with Vasoactive Intestinal Polypeptide and Acetylcholine in Parasympathetic Cerebrovascular Nerves Originating in the Sphenopalatine, OTIC, and Internal Carotid Ganglia of the Rat

Neuropeptide Y co-exists with noradrenaline in the majority of the sympathetic nerves supplying cerebral blood vessels. However, after sympathectomy in the rat the number of cerebrovascular neuropeptide Y nerve fibers are only reduced in number despite a complete disappearance of the adrenergic markers. The origin of these non-sympathetic neuropeptide Y fibers was studied by nerve transections and retrograde axonal tracing utilizing True Blue. Three days after bilateral superior cervical sympathectomy, the number of neuropeptide Y-containing nerve fibers decreased to about 40% of that in non-treated animals. One week after True Blue application on the proximal portion of the middle cerebral artery, the tracer accumulated in neurons of the sphenopalatine, otic, and internal carotid ganglia. Of these cells 80%, 95% and 5%, respectively, were neuropeptide Y-positive. Some of the True Blue/neuropeptide Y-positive cells displayed immunoreactivity for vasoactive intestinal polypeptide and some were positive for choline acetyltransferase. Two weeks after bilateral removal of the sphenopalatine ganglion or transection of postganglionic fibers from the ganglion reaching the pial vessels through the ethmoidal foramen, together with subsequent sympathectomy, no neuropeptide Y-containing nerve fibers could be observed on the anterior cerebral and internal ethmoidal artery or the distal portion of the middle cerebral artery, whereas a few nerve fibers remained on the proximal portion of the middle cerebral artery, internal carotid artery, and the rostral portion of the basilar artery. In conclusion, neuropeptide Y in cerebrovascular nerves is co-stored not only with noradrenaline in sympathetic nerves from the superior cervical ganglion, but also with acetylcholine (reflected in the presence of choline acetyltransferase) and vasoactive intestinal polypeptide in parasympathetic nerves originating in the sphenopalatine, otic, and internal carotid ganglia.

Neuropeptide Y (NPY)-containing nerves in mammalian ureter

The distribution of neuropeptide Yin the ureter of the rat, rabbit, and man has beendetermined by radioimmunoassay and chromatographic analysis of the tissue extract. The localization of neuropeptide Y-immunoreactivity has been identified by immunocytochemistry. A regional distribution of neuropeptide Y was found; highest concentrations being present in the ureterovesical junction. Throughout the ureter, neuropeptide Y-immunoreactive nerve fibers were identified to surround the blood vessels and a few plexuses of neuropeptide Y-containing nerves were present within the muscle layers. Neuropeptide Y was not present within ganglion cells. Treatment of rats hydroxydopamine resulted in a significant reduction of neuropeptide Y concentrations in the middle, and lower thirds of the ureter. This depletion in extractable neuropeptide Y was ted with morphologic changes typical of axonal degeneration of the neuropeptide Y-containing nerve fibers.

Perivascular innervation of the mesenteric artery in spontaneously hypertensive rats.

Perivascular innervation of the mesenteric arteries of 7-week-old and 6-month-old spontaneously hypertensive rats and normotensive Wistar-Kyoto rats was examined. The densities of neuropeptide Y-containing nerve fibers and adrenergic nerve fibers were increased in the distal regions of mesenteric arteries of spontaneously hypertensive rats as compared with findings in Wistar-Kyoto rats. However, the densities of cholinergic nerve fibers, vasoactive intestinal polypeptide-containing, and substance P-containing nerve fibers in the mesenteric arteries of the spontaneously hypertensive rats were unchanged in comparison with findings in the Wistar-Kyoto rats. Thus, not only adrenergic nerve fibers but also neuropeptide Y-containing nerve fibers may play an important role in the development and maintenance of hypertension in spontaneously hypertensive rats.

Peptide-containing nerve fibers in the respiratory tract of the ferret

The ferret is widely used in functional and neuromorphological studies on the respiratory tract. We have examined the occurrence and distribution of peptide-containing and adrenergic nerve fibers (using dopamine-beta-hydroxylase as a marker). Adrenergic nerve fibers and fibers storing vasoactive intestinal peptide have a widespread distribution along the entire respiratory tract. Adrenergic nerve fibers were found in the lamina propria, as well as around blood vessels and glands and in smooth muscle. Nerve fibers storing vasoactive intestinal peptide occurred in the epithelium, the lamina propria, around blood vessels and glands, and among muscle bundles. Substance P-, neurokinin A- and calcitonin gene-related peptide-containing nerve fibers predominated beneath and within the epithelium along the entire respiratory tract. Neuropeptide Y-containing nerve fibers were prominent among smooth muscle bundles and around glands. The blood vessels in the wall of the airways were richly supplied with peptide-containing nerve fibers and adrenergic fibers. Ganglia located over the outer or dorsal surface of the tracheal wall harbored vasoactive intestinal peptide-containing nerve cell bodies. Substance P and neurokinin A invariably coexisted in the same nerve fibers. Further, coexistence of substance P/neurokinin A and calcitonin gene-related peptide was observed in the nerve fibers associated with the epithelium. Vasoactive intestinal peptide, neuropeptide Y and occasionally also substance P coexisted in the population of nerve fibers associated with blood vessels and smooth muscle. Many adrenergic nerve fibers contained neuropeptide Y.

Immunohistochemical observation on neuropeptides around the blood vessel in feline dental pulp

Recent advances in immunohistochemistry have revealed the distribution of various neuropeptides in several mammalian dental pulps. These neuropeptides are substance P, neurokinin A, calcitonin gene-related peptide, vasoactive intestinal polypeptide, and neuropeptide Y. Nerve fibers showing immunoreactivity for these neuropeptides are mainly localized around the pulpal vessels, but some are apart from the blood vessel. The distribution of substance P-, neurokinin A-, and calcitonin gene-related peptide-containing nerve fibers is very similar; it appears that these three neuropeptides may be contained in the same nerve fibers. Denervation experiments indicate that substance P-, neurokinin A- and calcitonin gene-related peptide-containing nerve fibers originate from the trigeminal ganglion and that neuropeptide Y-containing nerve fibers come from the superior cervical ganglion. However, the exact origin of vasoactive intestinal polypeptide-containing fibers still remains unknown. These immunohistochemical data indicate that neuropeptides localized around the blood vessel may play a significant role in the regulation of the blood flow in the dental pulp.

Vagal paraganglia of the rat

Paraganglia are associated with every branch of the rat vagus nerve except the pharyngeal branch. Some of the paraganglia closely resemble the glomus caroticum, whereas others appear like small, intensely fluorescent (SIF) cells of autonomic ganglia. The paraganglionic cells of SIF cell-like bodies (SLB) store catecholamines (the most abundant is probably noradrenaline) and in some cases neurotensin. The innervation pattern of SLB is variable and their physiological role remains unclear. Paraganglionic cells of glomus-like bodies (GLB) predominantly store dopamine and probably also to a lesser extent noradrenaline. These putative chemoreceptor organs receive sensory innervation from nodose ganglion neurons as revealed by degeneration experiments and by anterograde neuronal tracing. Substance P- and calcitonin gene-related peptide-immunoreactive fibres seen in the region of vascular entry into the GLB may account for some of these sensory fibres, but the peptide/classical transmitter stored in sensory terminals synapsing on paraganglionic cells is unknown. Ultrastructural immunocytochemistry revealed vasoactive intestinal polypeptide (VIP)-immunoreactive fibres lying in the interstitial space between paraganglionic cells and large capillaries. These fibres may originate from VIP-immunoreactive neurons, being frequently attached to GLB. The major difference between GLB and the glomus caroticum concerns their blood supply and related innervation: Arteries and arterioles do not penetrate into GLB and, accordingly, noradrenaline- and neuropeptide Y-containing nerve fibres are lacking within GLB. This peculiar arrangement of paraganglionic parenchyma and arterial blood supply may be one of the reasons for the different physiological properties of vagal and carotid arterial chemoreceptors.

Distribution, possible origins and fine structure of neuropeptide Y-containing nerve fibers in the rat liver

The distribution, possible origins and fine structure of neuropeptide Y (NPY)-containing nerve fibers in the rat liver were investigated by immunohistochemistry, nerve transection and immunoelectron microscopy. Light-microscopic immunohistochemistry showed NPY fibers forming a complex network in and around the walls (tunica adventitia and tunica media) of hepatic vessels. They were also closely associated with interlobular bile ducts. The NPY fibers in the liver were almost completely eliminated by transection of the greater splanchnic nerves just distal to the celiac ganglion. Transection of the greater splanchic nerves just proximal to the celiac ganglion resulted in a marked decrease in NPY fibers, but a significant number remained intact. Under electron microscopy, NPY terminals without a covering of glial processes were seen not only in proximity to smooth muscle cells within the tunica media of hepatic vessels but also in the subendothelia areas of the tunica intima. Som NPY axon terminals devoid of glial enshethment were located close to the basal lamina of interlobular bile ducts. Occasionally, single axon terminals with NPY were found in the vicinity of or in contact with hepatic cells. There was a small number of NPY fibers that had lost their glial sheaths while running toward lymphatic capillaries. These findings suggest that hepatic NPY arises from the celiac ganglion and paravertebral sympathetic ganglia, and that it is involved in more complex physiological processes than the previously neuropeptides in the liver, which are localized exclusively to hepatic vessel walls.

Study of neuropeptide Y-containing nerve fibers in the human penis.

Neuropeptide Y 1-36 (IR-NPY) immunoreactive nerve-fiber processes have been observed in tunicae of veins and arteries and in smooth muscles of the human penis taken at autopsy or during surgery by use of light- and electron-microscopic immunohistochemical techniques. Numerous IR-NPY nerve fibers were mostly concentrated in the inner part of the adventitia close to the media of the arterial and venous vessels and among the intracavernous smooth muscle cells. IR-NPY nerve fibers were less abundant in veins than in arteries. Positive somata were not observed in the penises. At the ultrastructural level, IR-NPY were localized exclusively in large, dense granules of nerve terminals by means of the postembedding immunogold technique. In the deep dorsal vein, IR-NPY nerve fibers were also located in the media formed by an outer circular and an inner longitudinal layer. In the intracavernous and dorsal arteries, they showed the highest density in the inner part of the adventitia. In the corpora cavernosa and in the corpus spongiosum, IR-NPY nerve processes were intermingled between the smooth-muscle fibers around the sinusoid spaces. IR-NPY nerve fibers were present in the cavernous nerves close to the central arteries. The urethra did not show any IR-NPY-positive nerve fibers. This peculiar distribution of IR-NPY nerve fibers suggested that they could participate in regulating arterial and venous blood flow and intracavernous smooth-muscle tone. NPY may therefore be of importance in some of the mechanisms of penile erection especially during detumescence.