PubMed Health⌕ Search

Biomedical subjects

W Kummer

Publications and source records attributed to W Kummer.

At least 73 records · Page 4Linked to original sources
PubMed1995

Nitric oxide synthase and vasoactive intestinal polypeptide colocalization in neurons innervating the human penile circulation.

The question which neurotransmitters mediate penile erection in humans is still unsettled. Although functional studies have established a role of vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) in human penile smooth muscle relaxation, they did not allow a conclusion as to whether they are released by neurons or other cells. This article outlines the identification of numerous nitric oxide synthase (NOS) and VIP-containing axons in the human penis. More than 50% of the perivascular nerve fibres and more than 90% of the trabecular nerve fibres within the corpus cavernosum stained positive for both NOS and VIP. In contrast, endothelial cells stained only faintly for NOS-immunoreactivity, NOS/VIP-immunoreactivity was reduced (diabetes) or absent (lesion of the cavernous nerve) in penile tissue taken from patients with neurogenic impotence. These findings support the concept that NO and VIP act as neural comediators of penile erection in humans.

Humans↗
PubMed1994

A quantitative ultrastructural investigation of tyrosine hydroxylase-immunoreactive axons in the hairy skin of the guinea pig.

Besides its thermoregulatory role, the sympathetic innervation of the skin is involved in a modulation of sensory processing and trophic functions that has not been fully characterized. To investigate possible sites at which such sympathosensory interactions might occur, a quantitative ultrastructural study of the sympathetic innervation of the skin was attempted. The hairy skin of the guinea pig was studied because the sympathetic and sensory nerve axons in this species can easily be discriminated by the presence of immunoreactivity to the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH). The thermoregulatory role of the sympathetic skin innervation was highlighted by the almost exclusive sympathetic innervation of piloarrector muscles which contained 62% (n = 195) of randomly selected TH-immunoreactive (TH-IR) axon profiles. Of TH-IR pilomotor axons, 53% were filled with vesicles. Vesicle-containing axonal profiles were equally frequent around dermal arterial blood vessels (partly associated with mast cells), hair follicles, and within nerve fibre bundles surrounded by a perineural sheath, in each case accounting for about 3% of all dermal TH-IR axonal profiles. In contrast to piloarrector muscles, at these locations TH-IR (sympathetic) and non-reactive (sensory) axons were found in close association. These findings are in line with the previously reported inhibitory influence of sympathetic stimulation upon hair follicle afferents and perivascular sensory nerve terminals. In addition, they point to a yet underestimated target of sympathetic axon terminals, i.e. preterminal nerve fibre bundles.

Animals↗
PubMed1994

Nitric oxide synthase in the rat carotid body and carotid sinus.

The participation of nitric oxide synthase (NOS) in the innervation of the rat carotid body and carotid sinus was investigated by means of NADPH-diaphorase histochemistry and NOS immunohistochemistry using antisera raised against purified neuronal NOS and a synthetic tridecapeptide. NOS was detected in 23% of neurons at the periphery of the carotid bodies. Some negative neurons were surrounded by NOS-positive terminals. NOS-containing varicose nerve fibres innervated the arterial vascular bed and, to a lesser extent, the islands of glomus cells. These fibres persisted after transection of the carotid sinus nerve and are probably derived from intrinsic neurons. Large NOS-positive axonal swellings in the wall of the carotid sinus were absent after transection of the sinus nerve, indicating their sensory origin. The results suggest a neuronal nitrergic control of blood flow, neuronal activity and chemoreception in the carotid body, and an intrinsic role of NO in the process of arterial baroreception.

Amino Acid Oxidoreductases↗
PubMed1994

Nerve supply of anterior cruciate ligaments and of cryopreserved anterior cruciate ligament allografts: a new method for the differentiation of the nervous tissues.

We investigated the nerve supply of anterior cruciate ligaments ((ACLs) and of cryopreserved bone-ACL-bone allografts in a rabbit model with immunohistochemical methods to establish the distribution pattern of the nervous tissues and to determine the reinnervation rate of ACL allografts. The ACL is innervated by three different classes of nerve fibre: (1) fibres of large diameter, characterized by neurofilament immunoreactivity, which are fast-conducting mechanoreceptive sensory afferents; (2) fibres of small diameter, characterized by substance P-immunoreactivity, which are slow-conducting nociceptive sensory afferents; and (3) sympathetic efferent vasomotor fibres, characterized by their immunoreactivity to the rate-limiting enzyme of noradrenaline synthesis, tyrosine hydroxylase. The ACLs showed numerous fibres of all three nerve classes; as specialised sensory nerve endings only Ruffini corpuscles were observed. All nerve fibres were located subsynovially, none within the collagen core of the ligament itself. No nerve fibres were detected in the ACL allografts at 3 and 6 weeks. Sparse fibres were detected at 12 weeks, while the 24-, 36- and 52-week specimens showed plenty of all three fibre types. No mechanoreceptors were found in the ACL allografts. To our knowledge, this method for the first time allows a differentiation of the nerve fibres of ACLs and ACL allografts into three different nerve fibre classes with known neurophysiological functions.

Animals↗
PubMed1994

Sensory ganglia as a target of autonomic and sensory nerve fibres in the guinea-pig.

The distribution of neuropeptide- (neuropeptide Y, substance P, vasoactive intestinal peptide) and catecholamine-synthesizing enzyme-immunoreactive axons in guinea-pig trigeminal, nodose, and cervical dorsal root ganglia was studied by double-labelling immunofluorescence in controls and after extirpation of either the cervical sympathetic trunk or the stellate ganglion; tyrosine hydroxylase- and dopamine-beta-hydroxylase-immunoreactive terminals in dorsal root ganglia were ultrastructurally investigated. Six neurochemically identifiable axons innervated the trigeminal ganglion, five kinds were found in the nodose and dorsal root ganglia. Two of them (catecholaminergic with and without neuropeptide Y) were of sympathetic origin and, besides their termination at arteries, provided a direct innervation of capsule cells of the trigeminal and cervical dorsal root ganglia facing the subarachnoid space. Varicosities which were interpreted as being of sensory origin were equally numerous in all ganglia, whereas those being likely of parasympathetic origin decreased in numbers from the trigeminal to the dorsal root and nodose ganglia. It is concluded that the sensory ganglia are the target of postganglionic sympathetic, parasympathetic and primary afferent neurons, each of which are specifically organized with respect to the neurochemical phenotype and inter- and intraganglionic distribution. Among other targets, these "nervi gangliorum" appear to be intimately linked to the ganglionic capsular cells and meningeal sheaths facing the liquor spaces.

Animals↗
PubMed1994

Effect of catecholamine depletion and denervation on neuropeptide Y(NPY) and tyrosine-hydroxylase (TH) mRNA levels in rat sympathetic ganglia.

Neuropeptide Y (NPY) and noradrenaline (NA) are synthesized and stored in sympathetic nerves and concomitantly released in response to appropriate stimuli. The two substances have been reported to interact on various levels: postjunctionally, by mutually potentiating their vasoconstrictor effects, prejunctionally, by inhibiting each other's release. The possibility of an interaction on the levels of their synthesis was investigated in this study. Specific cDNA probes were used for the measurement of the steady state levels of the mRNAs encoding prepro-NPY and tyrosine hydroxylase (TH) in the superior sympathetic cervical and stellate ganglia of rats. Reserpine (5 mg/kg) was administered for inducing catecholamine depletion. This caused a large decrease in the NA content of the heart associated with an about 50% reduction in cardiac NPY levels. Ganglionic NPY and TH mRNA levels increased 3-6 fold as compared to vehicle treated animals. To determine whether this effect was due to transynaptic induction, superior cervical ganglia were decentralized in a subgroup of rats. Decentralized ganglia displayed significantly lower NPY and TH mRNA levels than intact ones. The response to reserpine was almost completely prevented by decentralization. These Observations indicate that the activation of gene expression of NPY and TH by reserpine depends on intact ganglionic innervation and is therefore reflexly mediated. Trans-synaptic induction may regulate NPY and TH mRNA levels also under basal conditions.

Animals↗
PubMed1994

Innervation of epi- and endoneurial compartments of rat facial, vagus and sciatic nerves as studied by double-labeling immunofluorescence.

The mediators of axon terminals innervating the blood vessels and connective tissue compartments of rat peripheral nerves (facial, vagus and sciatic nerve) were investigated by means of double-labeling immunofluorescence. Sympathetic noradrenergic/neuropeptide-Y-immunoreactive axons innervated epi- and endoneurial arterial blood vessels; noradrenergic fibers without neuropeptide Y immunoreactivity terminated in the endoneurium between the axons of the main nerve trunk. Presumably sensory nerve terminals immunoreactive to substance P/calcitonin gene-related peptide supplied epi- but not endoneurial arteries and arterioles, and ran freely in the endoneurial space. Axons immunoreactive to vasoactive intestinal peptide innervated epineurial blood vessels of the facial and vagus nerve but were absent from the vasa nervorum of the sciatic nerve. The findings are in line with the concept, based upon previous pharmacological experiments, of a tonic constrictory and dilatory innervation of vasa nervorum. However, as judged from the distribution patterns of the neurochemically distinct axonal populations, vascular segments of different connective tissue compartments (epi- versus endoneurial) and body regions (sciatic versus cranial nerves) are differentially addressed by each of these axonal populations. This might have implications for the development of region-specific neuropathies.

Animals↗
PubMed1994

Sympathetic noradrenergic fibers as the source of immunoreactive alpha-neoendorphin and dynorphin in the guinea pig heart.

Dynorphin and alpha-neoendorphin bind to the kappa subtype of opioid receptors and have been shown to inhibit the release of noradrenaline from cardiac sympathetic axons. The purpose of this study was to elucidate the endogenous localization of dynorphin and alpha-neoendorphin in the guinea pig heart. This goal was achieved by double- and triple-labelling immunofluorescence. Dynorphin- and alpha-neoendorphin-immunoreactive nerve fibers were numerous around coronary blood vessels and among cardiomyocytes. They also contained immunoreactivities to the rate-limiting enzyme of catecholamine synthesis tyrosine hydroxylase and to neuropeptide Y. These fibers disappeared in response to chemical sympathectomy (6-hydroxydopamine treatment). In contrast, substance P/calcitonin gene-related peptide-immunoreactive axons of sensory origin did not contain dynorphin and alpha-neoendorphin immunoreactivities and were unaffected by chemical sympathectomy. The findings demonstrate that immunoreactive dynorphin and alpha-neoendorphin are contained in postganglionic sympathetic nerve fibers innervating coronary blood vessels and cardiac muscle. Therefore, the inhibitory effect of these peptides upon noradrenaline release from the sympathetic terminal may well be an autoinhibitory feedback loop.

Animals↗
PubMed1994

Serotonin immunoreactivity in the carotid body of adult humans.

The distribution of serotonin immunoreactivity (-IR) was studied in adult human carotid bodies, obtained at post-mortem, using both the peroxidase-antiperoxidase method on paraffin sections and a double-labelling immunofluorescence on frozen sections. Antibodies against synaptophysin and protein gene product (PGP) 9.5 were used for identification of serotonin-IR cells. Serotonin-IR was demonstrable in the carotid bodies of adult humans and it was coexpressed mostly with synaptophysin or PGP 9.5 in type I cells. Some serotonin immunopositive type I cells were located in close proximity to capillaries. Serotonin-IR was also observed in a few endothelial cells.

Adolescent↗
PubMed1993

Long-lasting increase of nitric oxide synthase immunoreactivity, NADPH-diaphorase reaction and c-JUN co-expression in rat dorsal root ganglion neurons following sciatic nerve transection.

Changes of NADPH-diaphorase reaction (NDP) and nitric oxide synthase immunoreactivity (NOS-IR) in neurons of dorsal root ganglia (DRG) were investigated following transection and ligation of rat sciatic nerve. In untreated rats, 2.7% of L4/L5 DRG neurons were labelled by NDP. After 3 days, intensity of NDP and number of labelled neurons increased and reached a maximal level between 10 and 20 days in 26.8% neurons which persisted up to 50 days. After 150 days, 8.7% of DRG neurons were still labelled. In contralateral L4/L5 DRG, but not L1 and T10 DRG, the number but not the intensity of NDP labelled neurons slightly increased between 10 and 50 days. The patterns of NOS-IR and NDP were congruent. Ipsilaterally, 76% to 92% of NDP neurons showed co-expression with the c-JUN transcription factor which is supposed to play a crucial role in the regeneration process. NDP accumulated in the peripheral nerve stump and was increased in the superficial dorsal horn between 10 and 30 days, whereas motoneurons were not labelled by NOS and NDP.

Amino Acid Oxidoreductases↗
PubMed1993

Nitric oxide synthase in guinea pig lower airway innervation.

The inhibitory non-adrenergic non-cholinergic (i-NANC) innervation of the guinea pig airways was suggested to be mediated, at least partially, by nitric oxide (NO). The enzyme catalyzing the generation of NO and citrulline from L-arginine, nitric oxide synthase (NOS), was found to be identical with neuronal nicotinamide-adenine dinucleotide hydrogen phosphate (NADPH)-diaphorase. In the present study, we report the distribution of NOS in guinea pig lower airways and in vagal sensory and sympathetic ganglia as revealed by NOS immunohistochemistry and NADPH-diaphorase histochemistry. The distribution of NOS was identical using either technique and displayed a similar distribution pattern in all parts of the lower airways. Yet, the number of NOS-containing fibres was increasing from cervical trachea towards principal bronchi and decreasing to complete absence in bronchioli. Innervation with NOS-containing nerve fibres was densest in the smooth muscle layer and in the lamina propria of the mucosa. Single fibres were found in the respiratory epithelium. Labelling was absent from nerve fibres innervating the submucosal glands. Perivascular fibre networks enmeshed tracheal arteries, pulmonary arteries and veins. A substantial number of NOS-immunoreactive and NADPH-diaphorase-positive neurons was observed in vagal sensory ganglia, whereas such neurons were rather sparse in sympathetic ganglia. Tracheal and peribronchial ganglia of the airways were devoid of labelling. These findings suggest that extrinsic rather than intrinsic (tracheal and peribronchial) neurons are the source of NO release from guinea pig airway nerve fibres after electrical field stimulation. These extrinsic nerve fibres may originate from both sympathetic and vagal sensory ganglia.

Amino Acid Oxidoreductases↗
PubMed1993

Immunohistochemical evidence from co-localization and denervation studies for four types of substance P-containing nervous structures in the rat superior cervical ganglion.

Four types of substance P-immunoreactive structures have been distinguished in the rat superior cervical ganglion by double-immunofluorescence microscopy: (1) A major population of mainly varicose fibres enmeshed singly-scattered neuronal perikarya, some of which contained vasoactive intestinal polypeptide-immunoreactivity. These substance P-immunoreactive fibres did not contain colocalized calcitonin gene-related peptide (CGRP) and were absent after transection of the cervical sympathetic trunk. (2) A rather small substance P-immunoreactive fibre population with colocalized calcitonin gene-related peptide-immunoreactivity was distributed in a patchy manner and disappeared after cutting the postganglionic branches. (3) Most of the intraganglionic small intensely fluorescent (SIF) cell clusters were intensely substance P-immunoreactive. SIF cells were not visibly changed in number and fluorescence intensity by either surgical procedure. (4) Immunoreactivity was not visible in principal ganglionic neurons of control ganglia, but occurred in cell bodies after pre- as well as after postganglionic nerve transection. Some of the substance P-immunolabelled perikarya in addition revealed immunostaining to antisera against the catecholamine-synthesizin enzyme tyrosine hydroxylase or against the neuropeptides leu-enkephalin and vasoactive intestinal polypeptide, respectively. The results strongly suggest that, in addition to a substance P-containing preganglionic input (1), and a supply by substance P-containing sensory axon collaterals (2), the superior cervical ganglion of the rat gives origin to a paraganglionic (3) and a postganglionic (4) substance P-immunoreactive intrinsic system, the latter becoming visible only after disconnection of the sympathetic pathway.

Animals↗
PubMed1993

Tyrosine-hydroxylase-containing vagal afferent neurons in the rat nodose ganglion are independent from neuropeptide-Y-containing populations and project to esophagus and stomach.

Immunoreactivity to the rate limiting enzyme of catecholamine synthesis, tyrosine hydroxylase, has been described in the inferior sensory (= nodose) ganglion of the vagal nerve in the rat. The aim of the present study was to characterize further this neuronal population. The neurons do not represent displaced autonomic efferent neurons, since they do not receive synaptic input, as indicated by the absence of synaptophysin-immunoreactive terminals. In addition to the immunoreactivity to tyrosine hydroxylase, a tyrosine hydroxylase cRNA probe hybridizes with nodose ganglion neurons as demonstrated by in situ hybridization and Northern blotting. Many but not all of the tyrosine hydroxylase-immunoreactive neurons are also immunoreactive to the dopamine synthesizing enzyme, aromatic-L-amino-acid-decarboxylase, but lack the noradrenaline-synthesizing enzyme, dopamine-beta-hydroxylase, thus favoring synthesis of dopamine. Neuropeptide Y, which is often colocalized with catecholamines, is also present in a subset of nodose ganglion neurons, as indicated by immunohistochemistry, in situ hybridization and Northern blotting. However, double-labeling immunofluorescence has revealed that these two antigens are localized in different cell populations. Retrograde neuronal tracing utilizing fluorescent dyes (Fast blue, Fluoro-gold) combined with tyrosine hydroxylase immunohistochemistry has demonstrated that the esophagus and stomach are peripheral targets of tyrosine-hydroxylase-containing vagal viscero-afferent neurons.

Animals↗
PubMed1993

Immunohistochemical evidence for different pathways immunoreactive to substance P and calcitonin gene-related peptide (CGRP) in the guinea-pig stellate ganglion.

The colocalization of immunoreactivities to substance P and calcitonin gene-related peptide (CGRP) in nervous structures and their correlation with other peptidergic structures were studied in the stellate ganglion of the guinea pig by the application of double-labelling immunofluorescence. Three types of fibre were distinguished. (1) Substance P+/CGRP+ fibres, which sometimes displayed additional immunoreactivity for enkephalin, constituted a small fibre population of sensory origin, as deduced from retrograde labelling of substance P+/CGRP+ dorsal root ganglion cells. (2) Substance P+/CGRP- fibres were more frequent; some formed baskets around non-catecholaminergic perikarya that were immunoreactive to vasoactive intestinal polypeptide (VIP). (3) CGRP+/substance P- fibres were most frequent and were mainly distributed among tyrosine hydroxylase (TH)-immunoreactive cell bodies. The peptide content of fibre populations (2) and (3) did not correspond to that of sensory ganglion cells retrogradely labelled by tracer injection into the stellate ganglion. Therefore, these fibres are thought to arise from retrogradely labelled preganglionic sympathetic neurons of the spinal cord, in which transmitter levels may have been too low for immunohistochemical detection of substance P or CGRP. CGRP-immunoreactivity but no substance P-immunolabelling was observed in VIP-immunoreactive postganglionic neurons. Such cell bodies were TH-negative and were spared by substance P-immunolabelled fibre baskets. Retrograde tracing with Fast Blue indicated that the sweat glands in the glabrous skin of the forepaw were the targets of these neurons. The streptavidin-biotin-peroxidase method at the electron-microscope level demonstrated that immunoreactivity to substance P and CGRP was present in dense-cored vesicles of 50-130 nm diameter in varicosities of non-myelinated nerve fibres in the stellate ganglion. No statistically significant difference in size was observed between vesicles immunolabelled for substance P and CGRP. Immunoreactive varicosities formed axodendritic and axosomatic synaptic contacts, and unspecialized appositions to non-reactive neuronal dendrites, somata, and axon terminals. Many varicosities were partly exposed to the interstitial space. The findings provide evidence for different pathways utilizing substance P and/or CGRP in the guinea-pig stellate ganglion.

Animals↗
PubMed1993

Nitric oxide synthase-immunoreactive axons innervating the guinea-pig lingual artery: an ultrastructural immunohistochemical study using elastic brightfield imaging.

The ultrastructure of nitric oxide synthase-immunoreactive (NOS-IR) axons innervating the guinea-pig lingual artery was investigated by means of pre-embedding immunohistochemistry using an indirect peroxidase technique and diaminobenzidine. Sections ranging in thickness from 60 to 500 nm were ultrastructurally evaluated in elastic brightfield imaging mode. Thick sections (optimum at 300 nm) were advantageous for enhancement of the labelling intensity, whilst some subcellular details were better revealed by thin sections. NOS-IR axon terminals often contained aggregations of large, dense-cored vesicles, consistent with a previous light microscopical report on colocalization of NOS and vasoactive intestinal peptide-immunoreactivity in these fibres. NOS-IR axons formed direct neuro-muscular junctions (width less than 50 nm) at the outer surface of the tunica media, thus providing a structural basis for "nitrergic" vasodilation. In addition, NOS-IR axons made direct contacts with non-varicose and varicose segments of non-reactive axons, suggesting interneuronal communication between these elements.

Amino Acid Oxidoreductases↗