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Prostacyclin producing activity of human umbilical blood vessels in adrenergic innervated and non-innervated portions.

The present experiment was performed in order to clarify the significance of prostacyclin (PGI2) in the regulation of human umbilical blood flow. Distribution of adrenergic nerve fibers in umbilical cord was examined by means of a modification of the glyoxylic acid fluorescence histochemical technique. PGI2 producing activity in various portions of umbilical blood vessels was measured by platelet bioassay. Adrenergic nerve fibers were observed only in the region surrounding umbilical arteries at the fetal end of the cord. PGI2 producing activity of umbilical arteries was significantly lower in the innervated region than in the non-innervated region. There were no significant regional differences in umbilical vein which has no adrenergic innervation. The relationship between vascular PGI2 producing activity and adrenergic innervation, and the significance of PGI2 in the regulation of human umbilical blood flow are discussed.

Adrenergic Fibers↗

Morphological features of collateral innervation and supernumerary innervation in the skeletal muscles of presenile rats.

Using silver impregnation either with or without cholinesterase staining, this study was designed to investigate the morphological patterns of remodeling in both the arborization of axon terminals and in the subneural apparatus of the motor endplate in adult rats (3, 6, and 12 months old). The coincidental growth of the nerve terminal and muscle fiber was observed to continue, and the number of muscle fibers remained unchanged up to 12 months of age. In 12-month-old muscles, as compared with those of the younger subjects, the frequencies of 1) terminals with signs of degeneration, growth, or both, 2) denuded postsynaptic cholinesterase sites not associated with the overlying axon, 3) collateral innervation, and 4) supernumerary innervation, were all seen to have increased. The functional terminal innervation ratio was increased to 1.06. The characteristic features consisted of enhanced collateral formation by means of ultraterminal sprouting, and of multiple axons proceeding to an already innervated endplate. An imbalance between growth and degeneration in the motor endplates during the presenile stages is thus a likely stimulus for the particular compensatory changes to increase the size of the motor unit.

Aging↗

Noradrenaline (gamma) and ATP responses of innervated and non-innervated rat cerebral arteries.

1. The distribution of sympathetic adrenergic nerves on the rat middle cerebral artery and on the arterioles which originated from it was determined by use of gloxylic histochemistry. 2. Whereas the middle cerebral artery and proximal arterioles arising from this artery received a sympathetic innervation, the distal regions of the same arterioles were devoid of innervation. 3. The arteries and arterioles which were innervated were depolarized by noradrenaline in the combined presence of alpha- and beta-adrenoceptor antagonists. Those which were not innervated were not depolarized by noradrenaline. 4. ATP depolarized all arteries and arterioles examined. 5. These observations are discussed with respect to the similarities and differences between gamma-adrenoceptors and P2 purinoceptors.

Adenosine Triphosphate↗

Developing innervation of the chick heart: a histofluorescence and light microscopic study of sympthetic innervation.

The available descriptions of the development of sympathetic innervation of the chick heart conflict with the known sympathetic innervation of the adult chicken heart. The adult heart is innervated by bilateral sympathetic cardiac nerves originating from the first thoracic sympathetic ganglia. These nerves travel lateral and anterior to the lung and join the vagi just before entering the pericardium along the great vessels. Using catecholamine histofluorescence techniques and silver preparations, we have observed the development of the sympathetic cardiac nerves. The sympathetic cardiac nerves arise from the first thoracic sympathetic ganglia on the 7th day of incubation. They grow lateral and then ventral to the developing lungs to join the vagi, and are found in the bulbar region of the heart and atrium on the 10th day of incubation. FLuorescent cells without processes mark the course of the sympathetic cardiac nerves and are present in the bulbar region on the 10th day and thereafter. Sympathetic ganglion cells lose their fluorescence between day 8 and day 16 of incubation. This is presumably due to dilution of the transmitter in the rapidly increasing volume of cytoplasm in the sprouting neurons. Small intensely fluorescent (SIF) and adrenal medullary cells do not undergo a diminution of fluorescence during this period. SIF cells appear well differentiated at 16 days.

Animals↗

Neuronal pathways from group-I and -II muscle afferents innervating hindlimb muscles to motoneurons innervating trunk muscles in low-spinal cats.

Synaptic inputs to motoneurons innervating the back and abdominal muscles in the lumbar part of the body from low-threshold hindlimb muscle afferents were studied in unanesthetized low-spinal cats. At a stimulus intensity of 1.2-1.5x threshold (T), which was sufficient to activate only group-I afferents, the incidence of post-synaptic potentials (PSPs) was higher when stimulating proximal muscle nerves than when stimulating distal muscle nerves (e.g., 52% versus 22% for motoneurons innervating m. iliocostalis lumborum: Ilio MNs; 38% versus 18% for motoneurons innervating m. obliquus externus: OEA MNs). At 2-5 T, at which group-II as well as group-I muscle afferents were presumably stimulated, the PSP incidence increased irrespective of nerves stimulated (e.g., 76% for Ilio MNs; 60% for OEA MNs). The minimal central latencies of EPSPs evoked at 1.2-1.5 T ranged 0.8-16.7 ms for Ilio motoneurons and 1.4 -14.2 ms for OEA motoneurons, indicating that the connection between back and abdominal motoneurons and low-threshold afferents from the hindlimb muscle include a monosynaptic one. The latencies of IPSPs were longer and ranged 1.9-18.8 ms for Ilio motoneurons and 2.4-15.8 ms for OEA motoneurons. Input patterns from various hindlimb muscles varied among individual motoneurons, even though they were within the same motoneuron pool. Such synaptic organization seems to differ from that for the leg motoneuron pool. The overall projection pattern of low-threshold afferents from leg muscles to lumbar back and abdominal motoneurons nevertheless suggests that group-I afferent inputs are related to lateral and vertical movements, and that group-II afferent inputs control the stiffness of the trunk.

Afferent Pathways↗

The electric lobes of the electric ray (Torpedo marmorata) are innervated by GABAergic fibres: immunocytochemical evidence for dual innervation of electromotoneurons.

It is currently thought that the electric lobes of electric rays are innervated by a single neuronal system, the oval nucleus system. In the work reported here, the innervation of the electric lobes was studied with silver staining methods, acetylcholinesterase histochemistry and gamma-aminobutyric acid (GABA) immunocytochemistry. Two types of axon were observed in the lobes: thick GABA-immunonegative fibres, which originated from the oval nucleus, and thin GABAergic fibres of unknown origin, here reported for the first time. Electromotoneurons were strongly acetylcholinesterase-positive. Non-GABAergic and non-cholinergic neurons were observed in the oval nucleus, which is innervated by GABA-immunoreactive fibres. These results suggest that GABA may modulate electric discharge both directly, by GABAergic fibres that project to the lobes, and indirectly, by GABAergic fibres that project to the oval nucleus.

Acetylcholinesterase↗

A histochemical study of the adrenergic innervation of the rat pineal gland: evidence for overlap of the innervation from the two superior cervical ganglia and for sprouting following unilateral denervation.

The rat pineal gland receives sympathetic innervation, via the right and left internal carotid nerves, from neurons whose cell bodies are located in the two superior cervical ganglia. Using fluorescence microscopy, we have examined the density and distribution of fluorescent profiles in the pineal gland after lesioning of the internal carotid nerves. Thirty-two hours after sectioning both internal carotid nerves, the density of the fluorescent profiles was 3% of that seen in sham-operated controls, indicating that the lesioned fibers had degenerated. Thirty-two hours after sectioning one internal carotid nerve, the density of the processes was decreased to approximately 50% of the control value. The magnitude of the decrease following a unilateral lesion was similar on both the right and left halves of the gland. Thus, the results suggest that each internal carotid nerve innervates both sides of the pineal gland. The implications of this overlap in the innervation from the two internal carotid nerves for recovery of pineal function after a unilateral lesion are discussed. Sections of pineal glands were also analyzed at later time points after a unilateral lesion. Two weeks after cutting one internal carotid nerve, the density of the fluorescent profiles had increased to greater than 80% of the control value. When the contralateral internal carotid nerve was cut 2 weeks after a unilateral lesion and the pineal gland was examined 32 h later, the density of the fluorescent profiles had decreased to 2% of the sham value. This suggests that all of the compensatory increase in adrenergic processes that takes place following the unilateral lesion is due to sprouting of the contralateral internal carotid nerve rather than to regeneration of the lesioned internal carotid nerve or to sprouting and ingrowth of other adrenergic neurons. It remains to be determined what, if any, functional significance this sprouting has, since the neurally dependent circadian rhythm in serotonin N-acetyltransferase activity in the pineal gland is restored to normal within 32 h after a unilateral lesion; that is, before significant sprouting has occurred.

Acetyltransferases↗

Organization of the serotonergic innervation of spinal neurons in rats--III. Differential serotonergic innervation of somatic and parasympathetic preganglionic motoneurons as determined by patterns of co-existing peptides.

The spinal cord is innervated by brainstem serotonergic neurons, some of which contain substance P and/or thyrotropin-releasing hormone in addition to serotonin. These neurons project at least three types of axons to the spinal cord: those containing both substance P and thyrotropin-releasing hormone, those containing thyrotropin-releasing hormone but not substance P, and those containing neither substance P nor thyrotropin-releasing hormone. However, the organization of the different types of serotonergic processes is unclear. In the present studies, the types of serotonergic axons projecting to two kinds of spinal neurons were examined. Somatic and parasympathetic preganglionic motoneurons were labeled retrogradely from the pelvic or sciatic nerve, respectively. Sections containing these neurons were stained either for serotonin and substance P, or for serotonin and thyrotropin-releasing hormone. Of a total of 428 profiles examined that were retrogradely labeled from the sciatic nerve, 425 (99%) were apposed by serotonin-immunoreactive varicosities; similarly, of a total of 382 profiles examined that were retrogradely labeled from pelvic nerve, 353 (92%) were apposed by serotonin-immunoreactive varicosities. However, differences appeared to exist between the types of serotonergic varicosities innervating these two groups of neurons. Among the profiles labeled from the sciatic nerve, it was estimated that over 97% were apposed by serotonin-immunoreactive varicosities in which serotonin co-existed with substance P and thyrotropin-releasing hormone. In contrast, among the profiles labeled from pelvic nerve that were apposed by serotonin-immunoreactive varicosities, it was estimated that less than 1% were apposed by serotonin-immunoreactive varicosities containing both thyrotropin-releasing hormone and substance P. We estimate that most of the remainder (about 80%) were apposed by serotonin-immunoreactive varicosities containing thyrotropin-releasing hormone but not substance P. We conclude that both the cell bodies of neurons retrogradely labeled from the pelvic nerve and those labeled from the sciatic nerve were apposed by serotonin varicosities. However, these two systems of neurons appear to be innervated largely by two different populations of serotonergic cells. This suggests that the raphe-spinal serotonergic system may independently modulate the activities of somatic motoneurons and parasympathetic preganglionic motoneurons.

Animals↗

Innervation of the spleen in the rat: evidence for absence of afferent innervation.

Catecholaminergic fibers in the spleen have been well characterized in the rat and this innervation is believed to be an important source of modulation of the immune system. The presence or role of afferent feedback from the spleen has not been systematically investigated. We have examined whether the spleen receives afferent innervation from sensory ganglia and also have assessed the sources of efferent innervation to the spleen in the rat. The fluorescent retrograde anatomical tracers fluoro-gold (FGo) or fast blue (FB) were injected into the spleens of adult female rats and dorsal root, sympathetic chain, nodose, and celiac-mesenteric plexus ganglia were collected. In additional animals, the spleen was either injected with the anatomical tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP) or else regular HRP was applied to the cut end of the splenic nerve. Also, we examined the effects of cutting the splenic nerve on the retrograde labeling of cell bodies in the ganglia and on the catecholamine histochemistry of the spleen. The neuroanatomical results were based primarily upon the tracer FGo and verified that the celiac-mesenteric plexus ganglia provide a major efferent input to the spleen. Furthermore, lower thoracic sympathetic chain ganglia provide an additional and substantial efferent supply to the spleen. Cutting of the splenic nerve prevented retrograde labeling of cell bodies in the celiac-mesenteric plexus ganglia and sympathetic chain ganglia of rats injected with tracers into the spleen and also eliminated catecholamine histofluorescence in the spleen. In terms of afferent labeling, the results with FGo indicated that there were no cell bodies labeled in afferent ganglia following splenic injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidines↗

Is rabbit dentine innervated? A fine-structural study of the pulpal innervation in the cheek teeth of the rabbit.

The pulpal innervation of rabbit premolars and molars has been studied in transverse sections of perfusion-fixed, demineralised specimens using light microscopy and transmission electron microscopy. A mixed population of small myelinated and unmyelinated axons enters the apical foramen to supply the mesial and distal laminae of these continuously growing teeth. The nerve fibres are remote from the preodontoblasts and odontoblasts near the apical end, but in their passage to the occlusal end the pulp becomes progressively narrower and nerve fibres come to lie subjacent to the odontoblasts and postodontoblasts. Counts of myelinated fibres near the apical end and in the occlusal pulp suggested that the myelin is shed near the occlusal end. Most of the dentine in these teeth is tubular and migrates occlusally with supporting odontoblasts. Near the occlusal end, postodontoblasts deposit an atubular tissue which closes the pulpal ends of the tubules. Nearer the occlusal tip the pulpal contents degenerate and become embedded in the forming atubular tissue. Evidence of axon profiles was found near the occlusal end in the pulp, passing through the odontoblast layer and in the dentine tubules adjacent to odontoblast processes. However, many of the tubules contained an odontoblast process only and the atubular tissue was not innervated. Since innervated tubules eventually become closed by atubular tissue it is assumed that the nerve fibres retract from the tubules before their closure. In common with other teeth the function of the pulpal nerve supply is likely to be mostly nociceptive.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cerebral arterial innervation by nerve fibers containing calcitonin gene-related peptide (CGRP): I. Distribution and origin of CGRP perivascular innervation in the rat.

The origin, density and distribution of calcitonin gene-related peptide (CGRP) immunoreactivity in cerebral perivascular nerves and the trigeminal ganglion of rats were examined in this study. CGRP immunoreactive axons were abundant on the walls of the rostral circulation of the major cerebral arteries in the circle of Willis. The fibers form a grid- or meshwork of longitudinal and circumferential axons studded with numerous varicose swellings. The density of CGRP fibers was particularly high at the bifurcation of major arteries. A few CGRP fibers cross the midline to innervate arteries on the contralateral side of the arterial tree. The arteries of the caudal circulation were sparsely innervated by CGRP fibers. In the trigeminal ganglion, about 30% of the ganglion cells had CGRP immunoreactivity. The cell size of most (75%) of CGRP neurons was less than 30 micron in diameter. There was no significant difference in staining density between small and large CGRP neurons. Unilateral transection of the maxillary and mandibular divisions of the trigeminal nerve caused a substantial decrease of CGRP immunoreactivity in the ipsilateral dorsal two-thirds of the trigeminal nucleus and cervical spinal cord but did not noticeably change the diameter of the vascular lumen or the densities of CGRP fibers in the walls of the cerebral arteries. In contrast, unilateral transection that included the ophthalmic division eliminated CGRP fibers on the ipsilateral cerebral arteries and eliminated CGRP immunoreactivity throughout the trigeminal nucleus in the brainstem and rostral cervical cord. In addition, these lesions caused a significant reduction in the diameter of the denervated arteries. The present study demonstrates that CGRP, a putative neurotransmitter/neuromodulator, is especially abundant in the rostral cerebral circulation and is derived from the ipsilateral ophthalmic division of the trigeminal nerve. In addition, the loss of CGRP perivascular nerves is associated with a reduction of the arterial lumen. This suggests that CGRP is a strong candidate as a nerve-derived trophic factor at trigeminal terminals and provides additional evidence that CGRP is a component in the trigeminovascular system influencing vascular diameter.

Animals↗

Chick wing innervation. I. Time course of innervation and early differentiation of the peripheral nerve pattern.

Anterograde transport of horseradish peroxidase was used to map the initial projection patterns of motor and sensory axons innervating the wing of the chick embryo. Injections which resulted in labeling large numbers of motor and sensory axons, separately or in combination, were used to define the time course of innervation and to visualize the progressive morphogenesis of the peripheral nerve pattern. Motor axons emerged from the spinal cord and accumulated near the ventromedial border of the myotome where they remained for up to 16 hours before growing into the plexus region and limb bud. Despite the known later time of sensory neuron production, the first sensory axons projected to the wing at the same time as motor axons. When axons first entered the wing bud, they were distributed in two loosely organized sheets of axon fascicles, one projecting to dorsal muscle mass, the other to ventral muscle mass. The width of the sheets was between one-third to one-half the width of the wing bud, and this distance was more than twice the diameter of the proximal nerve trunks measured at stage 28. In the proximal limb the basic pattern of peripheral nerves emerged gradually from stages 26 to 28. During these stages, the loosely organized sheets of axonal fascicles seen at younger stages were progressively transformed into several coherent nerve trunks and muscle nerves extended from common nerve trunks. The implication of these observations is that many outgrowing axons appear not to follow preformed pathways corresponding to the mature peripheral nerve branching pattern. This pattern may instead result from axonal recognition of cues within a largely undifferentiated limb bud, and from the subsequent bundling together of loosely organized axon fascicles. These events occur concurrently with limb growth and differentiation.

Animals↗

Structure and innervation of the pineal gland of the rabbit, Oryctolagus cuniculus (L.). III. An electron microscopic investigation of the innervation.

In the rabbit pineal gland two types of postganglionic nerve endings were found which are characterized by the presence of small dense-core vesicles or small clear vesicles. Pharmacological and cytochemical experiments showed then to be noradrenergic and cholinergic, respectively. Both types were often present in the same nerve bundle, occasionally in close opposition. Intrapineal neurons were only rarely observed. They showed cholinergic synapses on their perikaryon and dendrites as well as noradrenergic axo-dendritic close contacts. Bilateral extirpation of the superior cervical ganglia revealed the postganglionic sympathetic origin of the pineal noradrenergic nerve fibres. Moreover, it appeared that these ganglia are hardly, if at all, involved in the pathway of pineal cholinergic innervation. The results obtained from lesions of both facial nerves, taken together with the results reported in the literature, led to the conclusion that the postganglionic cholinergic nerve fibers in the pineal are of parasympathetic origin. A model for the sympathetic and parasympathetic pineal innervation is proposed.

Acetylcholinesterase↗

Localization of parasympathetic preganglionic cell bodies innervating the pancreas within the vagal nucleus and nucleus ambiguus of the rat brain stem: evidence of dual innervation based on the retrograde axonal transport of horseradish peroxidase.

Traditionally studies have shown cell bodies of origin for parasympathetic preganglionic fibers of the subdiaphragmatic segment of the vagus nerve to be located in the dorsal motor nucleus of X. The nucleus ambiguus have been regarded as the motor nucleus for fibers projecting exclusively to larynx, pharynx and cervical esophagus. The results of the present study indicate that the pancreas has a dual source of innervation derived from both of these medullary nuclei, and that this in fact may be applicable for all or most of the subdiaphragmatic organs similarly innervated by the vagus.

Animals↗

Atrial natriuretic peptide in the innervation of the bovine heart conduction system: relationship with substance P and autonomic innervation--immunohistochemical studies.

Recently, we observed that atrial natriuretic peptide (ANP) immunoreactivity (IR) was present not only in the Purkinje fibres, but also in nerve fibre varicosities in the conduction system of the bovine heart. These findings and previous observations that ANP is able to influence autonomic neurotransmission in the heart, lead us to elucidate the possible occurrence of ANP in the sympathetic and/or parasympathetic nervous systems and/or in various types of peptidergic innervation in the conduction system. The different parts of the conduction system of bovine hearts were dissected out and processed for immunohistochemistry including double-staining, using antisera against ANP, tyrosine hydroxylase and different neuropeptides. We observed that some of the nerve fibre varicosities exhibiting ANP-IR showed substance P-IR and that ANP was present as scattered immunoreactive granules in intracardial, presumably parasympathetic, ganglionic cells. The study shows that ANP is likely to be present in parasympathetic innervation and in afferent nerve endings in the bovine heart conduction system.

Animals↗

Pineal serotonin metabolism in non-innervated perinatal glands before and after intraocular maturation: supersensitivity of adrenoceptors that have never been innervated.

Transplantations were made of fetal pineal glands (crown-rump length, CRL, 19-30 mm) or pineal glands from adult male rats to the anterior chamber of the eye of the rat. Studies were performed with regard to the importance of the age of the donor animal (and thereby the degree of maturation and innervation of the gland to be transplanted) for the possible development of denervation supersensitivity. The transplants were cultured in a medium containing 14C-serotonin. Increased production of 14C-N-acetylserotonin (NAcS) was used as the main criterion for beta-adrenergic stimulation. 4 experimental groups were obtained by transplanting fetal or adult pineals to intact or sympathetically denervated eyes. In all 4 groups beta1-stimulation (KWD 2033 10(-6) M) increased 14C-NAcS formation. The response to beta-stimulation was significantly higher in denervated fetal pineal transplants than in innervated fetal transplants and thus demonstrating beta-receptor supersensitivity. It was concluded that a) the ability to respond to beta-adrenoreceptor stimulation with increased 14C-NAcS formation develops between the 18th and 20th day of gestation, b) transplants derived from fetal as well as from adult rats can respond to beta-adrenergic stimulation, c) this sensitivity also develops in oculo in transplants that at the time of transplantation lacked the capacity to increase their 14C-NAcS formation in response to treatment with beta-agonist, d) denervation supersensitivity occurs in fetal transplants that became mature in sympathetically denervated eyes.

Animals↗

Innervation of bat heart: cholinergic and adrenergic nerves innervate all chambers.

Adult Miniopterus schreibersii were anesthetized with chloroform, and in vitro preparations of cardiac chambers were prepared. Stimulation of intramural nerves in right ventricles paced at 6 Hz caused an inhibition (56.3 +/- 3.5% decrease on basal force) mediated by cholinergic nerves and an excitation (91.5 +/- 9.9% increase on basal force) mediated by adrenergic nerves. Mean pD2s (-log effective concentration, 50%) for ventricular beta-adrenoceptors and muscarinic cholinoceptors were 6.99 +/- 0.03 and 6.42 +/- 0.07, respectively. The inhibition of ventricular contractility, by nerve stimulation or exogenous acetylcholine, occurred even after blockade of beta-adrenoceptors. The results were comparable to those obtained on atria. In some experiments, the heart was perfused in situ and paced via electrodes on the ventricle: stimulation of the right vagus nerve decreased right ventricular contractility by up to 90%. The results show that, at least in this hibernating mammal, there is an adrenergic innervation of the ventricle. The presence of a cholinergic vagal innervation capable of inhibiting the basal force of ventricular contraction has not been shown in any other mammal.

Animals↗

The innervation of the adrenal gland. III. Vagal innervation.

Following the injection of 3-5 microliters of horseradish peroxidase or Fast Blue into the left adrenal medulla, labelling of neurons in the vagal sensory ganglia of rats and guinea-pigs has been demonstrated in all cases. Labelled vagal motor neurons with cell bodies in the dorsal motor nucleus of the vagi have been demonstrated in all cases in the guinea-pig and occasionally in the rat. The possible reasons for this variation are discussed. In both rat and guinea-pig the motor and sensory vagal innervation of the rat adrenal is derived from bilaterally situated cell bodies and the proportion of innervation derived from the two sides is approximately equal but with a slight ipsilateral predominance.

Adrenal Glands↗