Search PubMed⌕ Search

Biomedical subjects

M Geffard

Publications and source records attributed to M Geffard.

At least 37 records · Page 2Linked to original sources

Non-dopaminergic catecholaminergic neurons of mesencephalic and medullary nuclei contain different levels of dopamine.

The present study addresses the question whether metabolic dopamine can be immunocytochemically detected within non-dopaminergic catecholaminergic axonal fibers. For this purpose, confocal microscopy was used to analyze sections treated for the double fluorescence immunostaining of dopamine and either noradrenaline or phenylethanolamine-N- methyltransferase (the enzyme in adrenergic neurons that converts noradrenaline into adrenaline). Our data demonstrate that throughout the brain and spinal cord, the majority of the axonal fibers that reacted with the anti-phenylethanolamine-N-methyltransferase antibodies also exhibited faint to intense dopamine immunoreactivity. Similarly noradrenaline and dopamine immunoreactivities were frequently colocalized within axonal fibers innervating brain and spinal cord regions that receive a dense innervation from medullary noradrenergic neurons. On the contrary, dopamine was rarely detected within noradrenaline-immunoreactive fibers in those regions where the noradrenergic innervation essentially arises from noradrenergic neurons of the locus coeruleus. A similar differential dopamine immunostaining was observed in the corresponding neuronal perikarya of the medulla oblongata and the locus coeruleus. These data indicate that two types of non-dopaminergic catecholaminergic neurons can be distinguished according to their content in dopamine: (i) the noradrenergic and adrenergic neurons located in the medulla oblongata, whose cell bodies and axons contain high concentrations of metabolic dopamine and (ii) the noradrenergic neurons located in the mesencephalon, which contain low levels of metabolic dopamine.

Adrenergic Fibers↗

Autoantibodies to malondialdehyde-modified epitope in connective tissue diseases and vasculitides.

Malondialdehyde (MDA), a peroxidative end-product released during polyunsaturated fatty acid degradation, reacts strongly with lysine residues of cellular proteins. MDA-modified proteins become immunogenic and may elicit specific autoantibody formation. We hypothesized that systemic diseases in which inflammatory events occur, could be an interesting model for studying oxidative stress. A few studies have suggested that MDA-modified proteins may exist in systemic diseases, and that autoantibodies to MDA-modified structures might reflect this oxidative process. Autoantibodies to MDA-modified epitope(s) were therefore assayed in sera of patients with systemic lupus erythematosus (SLE, n = 29), scleroderma (SCL, n = 11), giant cell arteritis (GCA, n = 11), periarteritis nodosa (PAN, n = 10), rheumatoid arthritis (RA, n = 9), and healthy subjects (HS, n = 32). Significantly increased anti-MDA-modified epitope(s) autoantibodies were found in patients with SLE and also in other systemic diseases such as PAN and SCL. Autoantibodies to MDA-modified epitope(s) were predominantly of IgM isotype, with low levels of IgG and no IgA activity. In SLE, anti-MDA-modified epitope(s) autoantibody titres correlated strongly with systemic lupus activity measure (SLAM, r = 0.702, P = 0.0001), anti-nuclear antigen autoantibodies (ANA, r = 0.4, P = 0.029), IgG anti-cardiolipin (r = 0.558, P = 0.03) and the steroid drug regimen (r = 0.52, P = 0.004). Autoantibodies to MDA-modified epitope(s) may reflect oxidative modifications occurring in systemic diseases, and might be useful as clinical markers of SLE activity if further investigated.

Adult↗

Octopaminergic dorsal unpaired median (DUM) neurones innervating the colleterial glands of the female cockroach Periplaneta americana

The musculature of the colleterial glands receives innervation from branch 4B4a of the nerves designated 4B, which arise from the posterior part of the terminal abdominal ganglion in the female cockroach Periplaneta americana (L). Using Methylene Blue staining, the gross anatomy of the colleterial gland innervation has been described. Cobalt backfilling via branch 4B4 of nerve 4B revealed about 21 dorsal unpaired median (DUM) neurones located on both median and posterior parts of the terminal abdominal ganglion. Octopamine immunohistochemistry has shown that at least 15 octopamine-immunoreactive DUM neurones from median and posterior groups projected via branch 4B4a to the left and right colleterial glands. These data, together with results reporting the presence of octopamine-immunoreactive branches supplying these colleterial glands, make octopaminergic DUM neurones suitable candidates to modulate the muscle activity of the colleterial glands in female Periplaneta americana.

Journal Article↗

Circulating antibodies directed against tryptophan-like epitopes in sera of patients with human African trypanosomiasis.

Human African trypanosomiasis is often associated with an intense proliferation of B lymphocytes, leading to polyclonal antibody synthesis. Using a modified enzyme-linked immunosorbent assay method, we have found highly significant levels of circulating anti-conjugated tryptophan-like epitope antibodies in sera of patients with sleeping sickness. These antibodies were immunoglobulins (Ig) of the M isotype. There was no correlation between immunologic binding and the Ig levels found in sera of patients with human African trypanosomiasis. Higher antibody levels in stage II of the disease than in stage I may be related to damage to the central nervous system. The specificity of this immunologic binding was evaluated by 1) comparison with that obtained with other related conjugates and 2) serum titration. Anti-conjugated tryptophan-like epitope antibodies were not found in other neurologic diseases tested. Their involvement in this pathology remains unknown.

Adolescent↗

Chemically induced sarcomas in Sprague-Dawley rats: dose effects on autoantibody levels and tumor progression.

We previously reported that a single injection of 2 mg benzo[a]pyrene (B[a]P) induced seric anti-phosphatidylinositol (PtdIns) autoantibodies (autoAb) and highly malignant sarcomas with 100% efficiency in Sprague-Dawley (SD) female rats. To evaluate the effects of lower doses, we administered a single dose (from 0.125 to 1 mg) of B[a]P into such rats. In all cases, we noted significantly high levels of anti-PtdIns autoAb, with clinically palpable tumors appearing around Day 100. Tumors grew more slowly than they did in the previous model (2 mg B[a]P). Both anti-PtdIns autoAb levels and first appearance of the tumor seemed to be independent of carcinogen doses. Conversely, tumor evolution seemed to depend on B[a]P doses.

Animals↗

Immunohistochemical evidence that central serotonin neurons produce dopamine from exogenous L-DOPA in the rat, with reference to the involvement of aromatic L-amino acid decarboxylase.

The aim of the present study is to examine whether aromatic L-amino acid decarboxylase (AADC) catalyzes the conversion of exogenous L-3,4-dihydroxyphenylalanine (L-DOPA) to dopamine in serotonin neurons of the rat dorsal raphe nucleus. First, in order to confirm the localization of AADC in central serotonin neurons, we used an immunoperoxidase method for AADC and demonstrated that the distribution of AADC-containing neurons in the dorsal raphe nucleus corresponds very closely to the previous description on the distribution of serotonin-immunoreactive neurons. Second, in the rat that received intraperitoneally L-DOPA plus a peripheral AADC inhibitor, we used a double-labeling immunofluorescence method and showed that serotonin-stained neurons of the dorsal raphe nucleus were also immunoreactive to dopamine. The present result suggests that AADC decarboxylating L-5-hydroxytryptophan to serotonin in physiological conditions is also able to catalyze the in vivo decarboxylation of exogenous L-DOPA.

Animals↗

Dopaminergic innervation of rat locus coeruleus: a light and electron microscopic immunohistochemical study.

Dopaminergic innervation of the rat locus coeruleus (LC) was immunohistochemically studied by using monoclonal antibody directed against dopamine (DA) at the light- and electron-microscopic levels. A dense plexus of DA-immunoreactive (IR) varicose fibers was found not only in the cell body area of the LC but also in the dendritic area. Three hundred and forty DA-IR terminal boutons were observed. They were distributed in a wide range of diameters of 0.1-1.8 microns but most of them were large (mean value: 0.98 micron). Sixty-nine percent formed an asymmetric synapse. There were many axo-spinous connections. Small dendrites less than 0.3 micron in diameter displaying synaptic specialization were mostly dendritic spines (75%). Most of the target dendrites seemed to be noradrenergic in nature. It is suggested that dopaminergic innervation may play a powerful role in control mechanisms of activity of NA-containing neurons of the LC.

Animals↗

Antibodies to reduced glutathione.

Reduced glutathione was conjugated to carrier proteins with glutaraldehyde. Conjugates were reduced by sodium borohydride and injected into rabbits. Using an enzyme-linked immunosorbent assay, antibody affinity and specificity were determined by competition experiments between glutathione conjugate and related conjugated compounds. The resulting cross-reactivity ratios, calculated at half-displacement, showed that conjugated glutathione was the best recognized compound. Non-reduced glutathione conjugate was 50 x less recognized. The other related conjugates were not recognized at all. Thus, the high affinity and relative specificity make these antibodies potentially valuable tools for immunohistochemical detection of reduced glutathione in glutaraldehyde-fixed rat brain. Using purified antisera diluted at 1/5000, reduced glutathione was preferentially visualized in nerve fibers of cortex, cerebellum and spinal cord. These results suggest that concentration of GSH in rat CNS are higher in nerve fibers than in neuronal perikaryons.

Animals↗

Host serotonin axons innervate intrastriatal ventral mesencephalic grafts after implantation in newborn rats.

This study investigated the potential of immature and adult serotonin (5-HT) neurons for axonal growth into intrastriatal grafts of ventral mesencephalic tissue. Implantation of dissociated fetal (embryonic days 14-15) ventral mesencephalic tissue was carried out in immature [postnatal days (P) 5-14] and adult rat neostriatum. The brains were processed 2-6 months later for dopamine and 5-HT immunocytochemistry. A few grafts implanted into adult and P7 recipients contained small numbers of cotransplanted 5-HT cell bodies. These also displayed a rich network of 5-HT axons, even in adult rats prelesioned with 5,7-dihydroxytryptamine, indicating the graft origin of these axons. All other grafts were totally devoid of 5-HT cell bodies. After implantation in adults, such grafts contained rare 5-HT axons. In contrast, in P5-P7 recipients, they displayed many 5-HT fibres, which were uniformly distributed. Such was no longer the case after implantation in P14 recipients, which showed minimal 5-HT innervation, as in adult recipients. Processing of naïve rat brain at different ages for 5-HT immunocytochemistry showed that 5-HT axons were still clearly less numerous in the neostriatum at P21 than in adults, whereas in the substantia nigra the 5-HT innervation developed more rapidly and was comparable, at P21, to that of adults. It was concluded that 5-HT axons are able to grow into ventral mesencephalic grafts, but mainly at the fetal stage and with decreasing capacity after birth.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗

Light and electron microscopic studies of the effects of p-chloroamphetamine on the monoaminergic innervation of the rat spinal cord.

A previous report has shown that small diameter serotoninergic (5-HT) axons innervating the forebrain are selectively eliminated by treatment with an amphetamine derivative, (+/-)p-chloroamphetamine (PCA; Mamounas et al., [1991] J. Comp. Neurol. 314:558-586). It is well known that the spinal cord is the target of numerous monoaminergic fibers of different types. We have previously shown that the dorsal and ventral horns and the intermediolateral cell column are innervated by numerous serotonin-, noradrenaline- and dopamine-containing axons, including both thin axons with small varicosities and beaded axons with large varicosities. In all these regions, the large majority of fine indolaminergic fibers do not establish synaptic contacts, contrasting with the beaded axons which mostly exhibit synapses. The present work was conducted to study the effect of PCA on the monoaminergic innervation of the adult rat spinal cord. Animals received two subcutaneous doses of PCA 24 hours apart and were perfused 3 weeks later. Immunocytochemistry was performed to detect 5-HT, noradrenergic and dopaminergic fibers by using light and electron microscopy. Light microscopy revealed that PCA treatment caused a marked and selective elimination of the fine 5-HT-immunoreactive fibers, mainly found in the dorsal horn, but spared all other larger axons. This selective effect on the dorsal horn innervating thin 5-HT fibers was confirmed with the electron microscope by calculating the synaptic incidence(s) of monoaminergic innervation. These results suggest that fine and beaded 5-HT axons correspond to two anatomically, biochemically and pharmacologically different types of fibers, which could arise from two subpopulations of brainstem neurons. In addition, this drug could be used to provide an experimental animal, devoid of 5-HT nonsynaptic fibers, thereby facilitating a study on the role of dorsal horn nonsynaptic system in pain modulation.

Animals↗

Synaptic connectivity of serotonin graft efferents in the suprachiasmatic and supraoptic nuclei of the hypothalamus.

We have previously reported that a cell suspension from the rostral part of the embryonic raphe grafted to the basal hypothalamus of 5,7-dihydroxytryptamine-denervated rats produced incomplete serotonin (5-HT) re-innervation of the suprachiasmatic nucleus (SCN) as opposed to hyper-innervation of the supraoptic nucleus (SON). We took advantage of this experimental model to investigate whether the graft-derived, 5-HT fibres retained normal ultrastructural features, and, particularly, a normal density of synaptic junctions, irrespective of the extent of target re-innervation. The intrinsic features of immunostained, graft-derived 5-HT axonal varicosities in both the SCN (ventral portion) and the SON were essentially similar to those exhibited by the respective endogenous innervation. Analysis of well-preserved varicosities in uninterrupted series of thin sections allowed us to evaluate directly the proportions of junctional to non-junctional 5-HT varicosities in both regions. Synaptic incidences were also remarkably conserved after grafting (45.5% in the SCN versus 38.5% in the SON; 48% and 38% in normal rats, respectively). Synapses were primarily reestablished on dendritic shafts, which also were identified as the major post-synaptic targets of the normal 5-HT innervations. We noted, however, a tendency toward increased numbers of symmetrical versus asymmetrical synapses in both the SCN and SON of grafted rats. Thus, irrespective of whether hypo- or hyper-innervation patterns developed post-grafting, the transplanted 5-HT neurons essentially retained normal ultrastructural features in their target territories, with a normal incidence of synaptic junctions. The data provide further support to the hypothesis that the innervation territory is the major determinant of the frequency with which ingrowing 5-HT fibres make synaptic junctions.

5,7-Dihydroxytryptamine↗

Neuritic GABAergic synapses in insect neurosecretory cells.

The localization of synaptic gamma-aminobutyric acid (GABA) receptors on cockroach dorsal unpaired median (DUM) neurons of the last abdominal ganglion was investigated. These neurosecretory cells, mainly octopaminergic, possess a soma located on the dorsal midline of the ganglion, from which emerges a short primary neurite dividing into two symmetrical lateral branches on both lateral edges of the ganglion. GABA pressure ejections onto the soma and onto the neuritic arborization elicited hyperpolarizations. Moreover, electrical stimulation of the anterior connectives evoked a postsynaptic potential, mainly inhibitory. This response and the GABA hyperpolarization of the neuritic field are antagonized by lateral application of picrotoxin while soma GABA hyperpolarization remained unchanged. This suggests that there are two kinds of GABA receptors located (i) onto the soma membrane of the DUM neurons and called extrasynaptic receptors, (ii) on the neuritic arborization, called synaptic receptors and implicated in the connection between neurons coming from the anterior part of the nervous system and the DUM cells. Immunohistological double staining technique reinforced the electrophysiological results by showing the presence of GABA-like immunoreactive processes next to octopamine-like immunoreactive ones.

Animals↗

Detection of putative dopamine receptors in neurites outgrowing from locust central nervous system explants using anti-idiotypic dopamine antibodies.

Organotypic cultures established from the third thoracic ganglion of locust embryo have been used to investigate dopamine receptors. In this in vitro system, neurites emerge directly from the explants and form a dense network around the explants, presenting cell surface freely exposed for experimental labelling. Polyclonal anti-idiotypic antibodies raised in rabbits to antibodies against dopamine conjugate, and previously found to bind to dopamine receptors, have been used to investigate putative dopamine receptors in these neurites. Immunocytochemical detection by light microscopy employing immunofluorescence labelling, was correlated with electron microscopy, using peroxidase staining. In addition to a location for dopamine receptors on the neurite surface, intracellular binding sites were also found in neurites. This internal labelling might represent an intracellular pool of dopamine receptor precursors. The labelling was specific in that it was not present when the anti-idiotypic dopamine antibodies were replaced with non-immune serum or when preincubation with conjugated dopamine preceded incubation with anti-idiotypic dopamine antibodies.

Animals↗

Dopamine neoinnervation in the substantia nigra and hyperinnervation in the interpeduncular nucleus of adult rat following neonatal cerebroventricular administration of 6-hydroxydopamine.

An aberrant network of dopamine axons was found to pervade the rat substantia nigra following neonatal destruction of its dopamine nerve cell bodies and dendrites by cerebroventricular administration of 6-hydroxydopamine. Light-microscopic immunocytochemistry with a primary monoclonal antibody directed against dopamine-glutaraldehyde-protein was used to investigate the time-course of development and the critical period of induction of this ectopic dopamine innervation (neoinnervation). In rats 6-hydroxydopamine-lesioned at postnatal day 3 (P3) and examined at P7, P10, P15, P30 or later, some dopamine fibers were already present in the substantia nigra at P7; their number increased sharply until P15 and only slightly thereafter, assuming a topographic distribution reminiscent of the missing dopamine nerve cell bodies and dendrites. A similar growth of dopamine fibers took place in the substantia nigra after lesions made at P6, P9 and P12, but was less pronounced after lesion at P15 and absent after lesion at P21 or later. Excessive innervation by dopamine axons (hyperinnervation) was concomitantly observed in the nearby interpeduncular nucleus. The sprouting of dopamine axons in both regions was therefore rapid and coincided in time and space with the developmental redistribution of mesencephalic dopamine neurons in normal rat. It is conceivable that these aberrant dopamine innervations play a role in the peculiar behavior and responsiveness to dopaminergic agents manifested by neonatally 6-hydroxydopamine-lesioned rats. It will be of particular interest to investigate the functional consequences of the dopamine neoinnervation in the substantia nigra, where an eventual axonal release might thus be replacing the normal somatodendritic release of this amine.

Aging↗

Baroreceptor-aortic nerve-mediated release of endogenous L-3,4-dihydroxyphenylalanine and its tonic depressor function in the nucleus tractus solitarii of rats.

We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter and/or neuromodulator in the central nervous system [Misu Y. and Goshima Y. (1993) Trends pharmac. Sci. 14, 119-123]. This study aimed to explore whether or not endogenous L-DOPA, as a neurotransmitter candidate of the primary baroreceptor afferents, tonically functions to activate depressor neurons in the nucleus tractus solitarii of anesthetized rats. By parallel microdialysis in bilateral nucleus tractus solitarii areas, the basal L-DOPA release was in part inhibited by tetrodotoxin perfusion (1 microM) or Ca2+ deprivation, and was markedly reduced by alpha-methyl-p-tyrosine (200 mg/kg, i.p.), a tyrosine hydroxylase inhibitor. Forty to 100 mM K+ concentration-dependently released L-DOPA. Fifty millimoles K+ repetitively and constantly released L-DOPA. This release was Ca(2+)-dependent. Stimulation of the left aortic nerve (100 Hz, 8 V) repetitively and constantly released L-DOPA and this release was tetrodotoxin-sensitive. Phenylephrine i.v. infused produced L-DOPA release and reflex bradycardia, temporally associated with a rise and subsequent recovery of blood pressure. This release and bradycardia were abolished by denervation of the bilateral carotid sinus and aortic nerves. In addition, L-DOPA methyl ester, a competitive L-DOPA antagonist, when microinjected into depressor sites of the left nucleus tractus solitarii, antagonized depressor responses to mild stimulation (20 Hz, 3 V) of the ipsilateral aortic nerve. This antagonist alone, microinjected bilaterally, elicited a dose-dependent hypertension, which was abolished by alpha-methyl-p-tyrosine. Furthermore, by immunocytochemical analysis seven days after denervation of the left aortic nerve, tyrosine hydroxylase- and L-DOPA-, but not dopamine- and dopamine-beta-hydroxylase-immunoreactivities decreased in the ipsilateral nucleus tractus solitarii and dorsal motor vagus nucleus complex area. In the left ganglion nodosum, denervation decreased staining and number of L-DOPA-immunoreactive cells and staining of tyrosine hydroxylase-immunoreactive cells, but no modification of dopamine-immunoreactive cells was seen. Taken together with previous findings that L-DOPA itself is stereoselectively responsible for cardiovascular control in this nucleus, it is probable that L-DOPA is a neurotransmitter of the primary baroreceptor afferents terminating directly in depressor neurons and/or indirectly in some neurons within a microcircuit, including depressor neurons of the nucleus tractus solitarii. Endogenously released L-DOPA itself tonically functions to activate depressor neurons for regulation of blood pressure in the rat nucleus tractus solitarii.

Animals↗

Curative effects on rat sarcomas obtained after a treatment combining two monoclonal antibodies.

The effects of a treatment involving two monoclonal antibodies (Ab) were evaluated on benzo(a)pyrene [B(a)P]-induced malignant sarcomas in Sprague-Dawley female rats. These Ab were, respectively, an anti-anti-conjugated B(a)P AB, an internal image of conjugated B(a)P, called AIB1, and an anti-conjugated L-DOPA Ab. They were biweekly injected into animals with small clinically palpable tumors. Anti-'phosphatidylinositol-like' autoantibody (autoAb) levels which were significantly higher in B(a)P-treated rat sera were decreased after Ab treatment. Tumor growth was slowed down compared with that of controls and animal survival was increased. This treatment was more efficient than that involving AIB1 alone. The anti-conjugated L-DOPA Ab may play a role in neovascularization, which is known to be critical for tumor growth.

Animals↗

Circulating autoantibodies directed against conjugated fatty acids in sera of HIV-1-infected patients.

Several reports have demonstrated that major changes occur in the fatty acid content of HIV-infected cells. In order to evaluate if these changes are recognized by the immune system, we have attempted to assay the possible presence of autoantibodies (autoAb) directed against conjugated fatty acids (CFA). Using an adapted ELISA, anti-CFA autoAb were assayed in sera of 150 HIV-1-infected patients and 116 controls (healthy donors and patients suffering from other diseases). Significantly increased anti-CFA autoAb of IgG class were found in HIV-1-infected patients (alpha < 0.001). Using our ELISA method and CFA differing in their length and their degree of unsaturation (lauric, myristic, palmitic, palmitoleic, stearic, oleic, linolenic, linoleic, lignoceric, arachidonic, eicosapentaenoic and docosahexaenoic acids), it was demonstrated that the acyl chain of CFA is the immunodominant part recognized by these autoAb. Anti-CFA autoAb were present in 15/52 asymptomatic carriers, 14/36 symptomatic carriers, 16/39 ARC patients, but only 3/23 AIDS patients. Anti-CFA activity seemed to be linked with the CD4+ T cell count, and was not related to the total IgG amounts. Anti-CFA autoAb could result from self-antigen presentation to immunological cells, and may reflect lipid membrane modifications occurring in HIV-infected cells.

Autoantibodies↗

Adrenergic innervation of the urinary bladder body in the cat with special reference to structure of the detrusor muscle: an immunohistochemical study of noradrenaline and its synthesizing enzymes.

The distribution of adrenergic nerves in the body detrusor muscle of the cat urinary bladder was studied by means of the immunohistochemical identification of noradrenaline (NA) and the NA synthesizing enzymes tyrosine hydroxylase, aromatic L-aminoacid decarboxylase and dopamine beta-hydroxylase. We identified the basic structural organization of the detrusor muscle, which had previously been described as lacking discernible layers. In the lateral wall, both outer longitudinal and inner circular muscle bundles were present, the latter extending in both anterior and posterior directions. The posteriorly running bundles came to lie on the outside of the posterior wall where they enabled recognition of inner longitudinal muscle bundles. Those running anteriorly were dispersed to enter the longitudinal bundles in the anterior wall. NA-immunoreactive nerve fibers in the detrusor muscle of the bladder were found to be similar to those immunoreactive for NA synthesizing enzymes in both distribution and density. In the upper and middle bladder body--including the dome (apex)--immunoreactive nerve fibers were always more abundant in the outer part of the detrusor muscle than in the inner part, regardless of the course of muscle bundles. Even in individual muscle bundles running from the inside to the outer surface, the outer part was more richly innervated by immunoreactive fibers than the inner part. In the bladder dome, a moderate number of immunoreactive nerve fibers preferentially innervated the outer part of the muscle layer. In the lower bladder body, these nerve fibers increased in density in the inner part of the detrusor muscle. There was no sexual difference in density or distribution of nerve fibers. NA- and NA synthesizing enzyme-immunoreactive nerve fibers were markedly decreased in number after 6-hydroxydopamine treatment. No dopamine- or phenylethanolamine-N-methyltransferase-immunoreactive nerve fibers were present in the bladder. The findings of this study indicate that the cat bladder musculature includes longitudinal and circular muscle bundles, both of which are extensively innervated by adrenergic nerves, particularly in the outer part of the bladder.

Adrenergic Fibers↗