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Biomedical subjects

E Weihe

Publications and source records attributed to E Weihe.

At least 109 records · Page 6Linked to original sources

Regional distribution of opioidergic nerves in human and canine prostates.

The regional distribution of opioidergic nerves in the juvenile and adult human prostate and in the adult canine prostate has been studied immunohistochemically using well-characterized polyclonal antisera against multiple opioid peptides. Nerves displaying immunoreactivity (ir) for the proenkephalin (PRO-ENK) derivatives met-enkephalin (ME), leuenkephalin (LE), octapeptide, and heptapeptide (ordered in decreasing frequency) were present in the dorsolateral stroma of human prostate. In canine prostate, the situation was similar, but the number of opioid-ir nerve fibers was lower than in human prostate. In both species, staining for the prodynorphin (PRO-DYN) derivatives dynorphin A and alpha-neoendorphin or staining for the pro-opiomelanocortin (POMC)-derived beta-endorphin was not visualized. In addition to their presence in nerve fibers, PRO-ENK-ir opioids (octapeptide) occurred in intrinsic ganglionic cells situated in the capsule. Octapeptide but not LE-ir fibers supplied stromal blood vessels. The periurethral region and tissue adjacent to the ejaculatory ducts appeared to be devoid of opioid-ir innervation. We conclude that endogenous opioids apparently exclusively derived from PRO-ENK may fulfill important comessenger functions in the fine regulation of prostatic stromal tonus and of local vascular perfusion.

Adolescent↗

Atrial natriuretic factor-like immunoreactivity in spinal cord and in primary sensory neurons of spinal and trigeminal ganglia of guinea-pig: correlation with tachykinin immunoreactivity.

Atrial natriuretic factor (ANF) is a cardiac hormone with various functions in body homeostasis. It is also processed in the brain and in the peripheral nervous system where it appears to play a role as a neuromodulator. Little is known about the presence of ANF throughout the spinal cord of the guinea-pig. We therefore examined the distribution of ANF and its possible interrelation with primary sensory afferents in this species. Using enzyme-and fluorescence-immunohistochemistry on deparaffinized sections. ANF-like immunoreactivity was found to be present in nerve fibers in laminae I/II of the spinal cord and in neurons of spinal and trigeminal ganglia. Tachykinins and ANF coexisted in very few fibers of the spinal cord but did not coexist in primary sensory spinal or trigeminal neurons. Our results indicate that spinal ANF-immunoreactive fibers are of dual origin, primary sensory and non-primary sensory. The possibly heterogeneous source of the non-primary sensory ANF, its possible coexistence with other co-transmitters and functional implications are discussed.

Animals↗

Induction of the gene encoding pro-dynorphin by experimentally induced arthritis enhances staining for dynorphin in the spinal cord of rats.

The response of dynorphinergic neurons in the lumbosacral spinal cord of the rat to chronic arthritic inflammation was studied by the combined use of biochemical and immunohistochemical procedures. In polyarthritic rats, in which all four limbs showed a swelling, inflammation and hyperalgesia, a pronounced elevation was seen in the level of messenger ribonucleic acid encoding prodynorphin (pro-enkephalin B) in the lumbosacral spinal cord. In addition, the levels of immunoreactive dynorphin A1-17, a primary gene product of this precursor, were greatly increased. This activation was reflected in a striking intensification of the immunohistochemical staining of both dynorphin and alpha/beta-neo-endorphin, a further major product of pro-dynorphin. In control animals perikarya were stained exceedingly rarely and encountered only in laminae I and II. Stained fibres and varicosities were seen throughout the dorsal and ventral gray matter, being most concentrated in laminae I, II, IV and V of the dorsal horn and dorsolateral to the central canal. In polyarthritic rats, fibres and varicosities were much more intensely stained throughout the cord, particularly in laminae I/II, IV and V and dorsolateral to the central canal. Many strongly-stained perikarya could be seen: these comprised many small diameter cells in laminae I and II, and some large diameter marginal neurons and large diameter cells, heterogenous in appearance, in the deeper laminae IV and V. Monolaterally inflamed rats injected in the right hind-paw showed pathological changes only in this limb. Correspondingly, in unilateral inflammation, an elevation in immunoreactive dynorphin was seen exclusively in the right dorsal horn and the above-described intensification of staining for dynorphin and neo-endorphin was seen only in this quadrant. This reveals the neuroanatomical specificity of the response. Thus, in the lumbosacral cord of the rat, pro-dynorphin neurons are most preponderant in laminae I, II, IV and V. A pronounced intensification of the immunohistochemical staining of these neurons is seen in chronic arthritis. Furthermore, there is a parallel elevation in the levels of messenger ribonucleic acid encoding pro-dynorphin and of its primary products dynorphin and neo-endorphin. These findings demonstrate an enhancement in the functional activity of spinal cord localized dynorphin neurons in the response to chronic arthritic inflammation.

Animals↗

Chromogranin A in the mammalian Merkel cell: cellular and subcellular distribution.

Chromogranin-A (CGA), which accounts for more than half the soluble matrix protein in secretory granules of various neuroendocrine cells, has a wide spectrum of potential biological roles and is considered an important marker of the diffuse neuroendocrine system (DNES). Light and electron microscopic immunohistochemistry of mammalian skin revealed that Merkel cells are exclusively CGA-immunoreactive (ir) and that the immunoreaction is localized in the secretory granules. This finding supports the classification of the Merkel cell as a member of the DNES. The CGA immunoreactivity was restricted to Merkel cells of pigs and humans. In human embryonic skin, CGA was expressed in Merkel cells as early as week 11 of gestation. The antisera differed in their ability to stain Merkel cells in different species and developmental stages, reflecting a variable chemical coding for CGA. CGA probably represents a precursor for smaller regulatory peptides or acts as a messenger on its own on various target tissues, suggesting a neurosecretory function of the Merkel cell.

Age Factors↗

Immunohistochemical analysis of chromogranin A and multiple peptides in the mammalian Merkel cell: further evidence for its paraneuronal function?

By the use of light microscopic immunohistochemistry, epidermal Merkel cells have been examined for the coexistence of some neuropeptides and chromogranin A (CGA). Peptide and CGA-immunophenotypes were similar in adult Merkel cells but variable in fetal skin, where CGA preceded the expression of peptides which were partly expressed only in a subpopulation of Merkel cells from hair follicles. Thus, only Substance P (SP) and calcitonin gene-related peptide (CGRP) were expressed in a subpopulation of Merkel cells from hair follicles. There were similar Merkel cell densities visualized on consecutive paraffin sections by the use of antisera against peptides, CGA and cytokeratin offering useful tools for a future systematical complementary mapping of Merkel cell populations in various species, locations and developmental stages. Electron microscopic immunohistochemistry has shown that CGA-immunoreaction is localized in the secretory granules which, again, supports the view that the Merkel cell is a paraneuron, i.e., neurosecretory in function.

Animals↗

Multiple neuropeptides in nerves supplying mammalian lymph nodes: messenger candidates for sensory and autonomic neuroimmunomodulation?

By the use of light microscopic (LM) immunohistochemistry, the presence of peptides and of dopamine beta-hydroxylase (DBH) in nerves supplying mammalian (guinea pig, rat, cat, pig, mouse, human) lymph nodes were examined. In all species, lymph nodes of various somatic and visceral regions were found to contain nerve fibers which stained for neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), substance P (SP), calcitonin gene-related peptide (CGRP) or DBH. SP- and CGRP-immunoreactive (ir) fibers completely overlapped and exhibited the widest distribution. They were present in perivascular, paravascular and many non-vascular fibers travelling in close contact with lymphoid cells. In contrast, NPY-ir fibers coincided with those staining for DBH, prevailed in perivascular plexus and only rarely branched off into lymphoid parenchyma. Alternate staining of adjacent sections revealed that SP/CGRP-ir fibers were different from NPY/DBH-ir fibers. The distribution of VIP-ir fibers was identical to that of PHI-ir fibers and partially overlapped with that of ir-NPY/DBH or ir-SP/CGRP fibers. We conclude that the NPY innervation of lymph nodes is sympathetic noradrenergic while nerves coding for co-existing SP and CGRP are most likely of sensory origin. The nerves containing co-existing VIP and PHI may be of heterogenous origin (sensory, cholinergic sympathetic, and/or parasympathetic). We suggest that these distinct sensory and autonomic peptidergic pathways linking the nervous system with the lymph nodes may play a differential role in bidirectional neuroimmunomodulation.

Adrenergic Fibers↗

Presence and coexistence of chromogranin A and multiple neuropeptides in Merkel cells of mammalian oral mucosa.

By the use of light microscopic (LM) immunohistochemistry, Merkel cells of the mammalian oral mucosa have been examined for the presence and coexistence of some neuropeptides and of the neuroendocrine marker chromogranin A (CG-A). Peptide and CG-A immunophenotypes of oral Merkel cells were found to vary between species and to depend on the developmental stage, as exemplarily revealed in the pig. Oral Merkel cells of adult cat, mouse and pig but not those of adult guinea pig stained for calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI). Pairs of adjacent sections alternately stained for SP, CGRP, VIP, PHI or for CG-A revealed mutual coexistence of these peptides and of CG-A (if expressed) in individual Merkel cells of hard palate, gingiva and buccal mucosa. CG-A immunoreactivity was restricted to Merkel cells of cat and pig. In adult pig and cat, a much lower number of Merkel cells stained for CG-A and peptide expression was inverse. These results indicate that the chemical coding of Merkel cells in mammalian oral mucosa is much more complex than previously described and depends on the developmental stage.

Animals↗

Co-localization of proenkephalin- and prodynorphin-derived opioid peptides in laminae IV/V spinal neurons revealed in arthritic rats.

By the use of highly selective antisera and an immunohistochemical technique the possible coexistence of proenkephalin- (PRO-ENK)- and prodynorphin (PRO-DYN)-derived peptides was examined in 4- to 6-micron thick serial sections of the L4-L5 segments of the spinal cord of non-colchicine-treated polyarthritic rats. In control, non-colchicine treated animals, virtually no cell bodies stained for the PRO-ENK-derived peptides, heptapeptide (MRF) and octapeptide (MRGL), nor for the PRO-DYN-derived peptides, dynorphin A (DYN) and alpha-neoendorphin (NEO). In contrast, in polyarthritic rats, numerous large (15-30 micron) multipolar neurons could be visualized with each antiserum in laminae IV/V. Alternate staining of adjacent sections with either anti-MRF or anti-MRGL antisera, followed by either anti-DYN or anti-NEO antisera, revealed a clear coexistence of PRO-ENK and PRO-DYN peptides. It was possible to demonstrate co-localization of all 4 opioids in a single cell. It appeared that all cells staining for PRO-ENK peptides in laminae IV/V also stained for PRO-DYN peptides.

Animals↗

Immunohistochemical evidence for the presence of peptides derived from proenkephalin, prodynorphin and proopiomelanocortin in the guinea pig pineal gland.

By using a plethora of region-specific antisera, this light microscopic immunohistochemical study revealed that derivatives from the three opioid precursors, i.e. proenkephalin, prodynorphin and proopiomelanocortin are differentially distributed in the pineal gland of guinea pig. Various molecular forms of immunoreactive opioid peptides derived from proenkephalin or prodynorphin were present in a minority of pinealocytes as well as in nerves. In contrast to this dual distribution pattern of opioid-active peptides, the opioid-inactive derivative from proopiomelanocortin, alpha-melanocyte stimulating hormone, was exclusively present in a large proportion of pinealocytes. A multiple and differential origin and function of opioidergic pineal innervation involving sympathetic, parasympathetic and sensory components is suggested. alpha-MSH is proposed as a pineal hormone which may act in concert with melatonin to regulate pineal rhythms or may function like MSH of pituitary origin.

Animals↗

Peptide neuroanatomy of adjuvant-induced arthritic inflammation in rat.

The influence of adjuvant-induced arthritis of the rat on central and peripheral peptide neuroanatomy was investigated by immunohistochemistry. The most striking feature of arthritic rats was the differential intensification of neuronal proenkephalin- and prodynorphin-related staining in dorsal horn. Changes were ipsilateral in monoarthritic and bilateral in polyarthritic rats as compared to controls. Opioid responsive neurons were target of substance P (SP) and calcitonin gene-related peptide (CGRP) fibers. Changes of SP and CGRP predominated in peripheral inflamed tissue and consisted of intensified immunostaining and an apparent sprouting of sensory fibers particularly around venules, in the epidermis and in areas infiltrated by immunocompetent cells. Opioid staining was absent from primary afferents but present in some immune cells of inflamed tissue. Endogenous antinociceptive opioids and pro-nociceptive/pro-inflammatory SP and CGRP may be crucial in the concerted response of the neuroimmune system to chronic inflammatory pain.

Animals↗

Co-existence of prodynorphin--opioid peptides and substance P in primary sensory afferents of guinea-pigs.

Light microscopic immunoenzymatic and immunofluorescence histochemistry revealed co-existence of opioid peptides with substance P in primary sensory neurons of all segmental dorsal root and trigeminal ganglia of guinea-pig. Sensory opioid peptides appeared to be exclusively processed from prodynorphin and include [Leu]enkephalin, neoendorphins, and dynorphin A. We suggest the presence of presynaptic opioid autoreceptors in primary sensory afferences.

Afferent Pathways↗

Prodynorphin opioid peptides in small somatosensory primary afferents of guinea pig.

By the use of light microscopic immunohistochemistry it was shown that a significant population of small primary sensory afferents of guinea pig contains immunoreactivities to antisera directed against prodynorphin-opioid peptides, whereas immunoreactivities to antisera directed against opioid peptides exclusively contained in proenkephalin were absent. Immunoreactivities to antisera against different prodynorphin-opioid peptides were seen in small ganglionic cells and in small diameter fibers of spinal and trigeminal ganglia, of dorsal roots, of somatic peripheral nerve trunks and in cutaneous sensory nerves. There was evidence for colocalization of different prodynorphin-opioid peptides. High-performance liquid chromatography and the mouse vas deferens assay revealed opioid-active material (22.7 pmol Met-enkephalin equivalents per gram wet weight) in extracts of somatic peripheral nerves. The results indicate for the first time that opioid peptides derived from prodynorphin are peripheral and central neurotransmitter candidates of small primary somatosensory afferents.

Animals↗

Proenkephalin- and prodynorphin- derived opioid peptides in guinea-pig heart.

Consecutive high performance liquid chromatography (HPLC) fractionation and the mouse vas deferens assay were used to characterize opioid peptides in the guinea-pig heart. Atria were found to contain at least nine different opioid peptides derived from proenkephalin and prodynorphin. In ventricles at least seven different molecular species which may be derived only from prodynorphin were present. The total opioid activity in atria averaged 22 pmol and in ventricles 11 pmol [Met]enkephalin equivalents per g wet wt. The high content of [Leu]enkephalin in relation to [Met]enkephalin indicates the possibility of a dynorphinergic pathway of cardiac [Leu]enkephalin. Multiple cardiac opioid ligands and receptors, including kappa, may be functionally important in the peripheral control of cardiac performance and coronary circulation.

Animals↗

Distribution of vasoactive intestinal polypeptide-like immunoreactivity in the mammalian heart. Interrelation with neurotensin- and substance P-like immunoreactive nerves.

The distribution of vasoactive intestinal polypeptide (VIP) immunoreactivity has been studied in the mammalian heart and compared with that of neurotensin and substance P by use of light-microscopic peroxidase-antiperoxidase immunohistochemistry. VIP-immunoreactive cell bodies are present in intracardiac ganglia in various locations. VIP-immunoreactive nerve fibers predominate in the atria and the conduction system but are rare in the ventricles and occur in cardiac ganglia, endocardium, and epicardium. VIP-ergic nerves supply the coronary vasculature having a preference for the microvasculature and the nodal cells of the sinuatrial node. The large vessels of the heart and periarterial cardiac glomera also receive a VIP-immunoreactive nerve supply. There is partial co-distribution with neurotensin- and substance P-immunoreactive nerve fibers but no co-location in identical nerve fibers is detectable. The VIP-ergic cardiac innervation, which is probably predominantly intrinsic, may stem from postganglionic parasympathetic neurons and is less substantial than the more homogeneous neurotensin-ergic and substance P-ergic nervous supply which is probably extrinsic. The occurrence of an extrinsic VIP-ergic cardiac innervation cannot be excluded however. The differential histotopography of the multitarget cardiac nerves containing the cardiovascular active peptides VIP, neurotensin and substance P may suggest multiple and complex peptide-peptide and peptide-classical transmitter interactions. These may contribute to the regulation of various cardiac functions.

Animals↗