Bilateral irradiation of head and neck induces an enhanced expression of substance p in the parasympathetic innervation of the submandibular gland

Forsgren, Sture; Franzén, Lars; Funegård, Ulrika; Gustafsson, H.; Henriksson, Roger

doi:10.1016/0306-4522(92)90023-u

Cited by 28 publications

(9 citation statements)

References 29 publications

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“…Recently Forsgren et al (1992) and Franzen et al (1993) reported an increase in the number of SP-and ENK-immunoreactive periacinar nerve fibers in the rat salivary glands 10 days after cessation of the irradiation procedure. Since reports of previous immunohistochemical studies on the human submandibular gland do not include a precise description of the conditions of the patients, it is not known whether the variance in the occurrence of immunoreactive fibers observed in previous studies is due to radiotherapy.…”

Section: Discussionmentioning

confidence: 97%

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Distribution of neuropeptide-containing nerve fibers in the human submandibular gland, with special reference to the difference between serous and mucous acini

Kusakabe

Matsuda

Kawakami

et al. 1997

Cell and Tissue Research

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Distribution of neuropeptide Y (NPY)-, vasoactive intestinal polypeptide (VIP)-, galanin (GAL)-, substance P (SP)-, and calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the human submandibular gland was examined by the peroxidase-antiperoxidase method with attention to high-quality fixation and the condition of patients. NPY-, VIP-, and GAL-immunoreactive varicose fibers were densely distributed around the acini and ducts. Some of these fibers extended between acinar cells. The density of SP- and CGRP-immunoreactive fibers was relatively low. The number of NPY-, VIP-, and GAL-immunoreactive fibers around the mucous acini was significantly higher than around the serous acini. In the perivasculature, NPY-immunoreactive fibers were more numerous than other immunoreactive fibers. No somatostatin-, leucine-, or methionine-enkephalin-immunoreactive fibers were detected. Our findings suggest that a large number of periacinar VIP-, NPY-, and GAL-immunoreactive fibers may participate in regulating the synthesis of saliva and its secretion. Since the VIP-, NPY-, and GAL-immunoreactive fibers are more numerous around the mucous acini than around the serous ones, these fibers may take part more actively in regulating the secretory mechanisms in the mucous acini than in the serous ones. The relatively low number of CGRP- and SP-immunoreactive fibers suggests that they are less involved in the function of the human submandibular gland. Perivascular peptidergic fibers, especially NPY-immunoreactive fibers, may be involved in controlling local blood flow in this gland.

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Section: Discussionmentioning

confidence: 97%

“…The previous studies have not considered these aspects. In order to reliably interpret results obtained with human tissues, it is necessary to take in account the condition of the patients; Forsgren et al (1992) and Franzen et al (1993) have recently found that irradiation has an effect on the fluctuation of neuropeptide immunoreactivity.…”

Section: Introductionmentioning

confidence: 99%

Distribution of neuropeptide-containing nerve fibers in the human submandibular gland, with special reference to the difference between serous and mucous acini

Kusakabe

Matsuda

Kawakami

et al. 1997

Cell and Tissue Research

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“…Thus, we recently observed an enhanced expression of substance P, but not CGRP, in the rat submandibular gland and ganglia ten days after bilateral irradiation to the head and neck (Forsgren et al, 1992). Furthermore, the pattern of expression of VIP and NPY in these structures did not change in response to such a treatment protocol (Franz6n et al, 1993).…”

Section: Discussionmentioning

confidence: 97%

Effects of irradiation on neuropeptide expression in rat salivary gland and spinal cord

et al. 1994

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It is well-known that a large number of factors can influence the expression of neuropeptides in the nervous system. In the present study, the effects of unilateral and bilateral irradiation to the rat head and neck on the expression of neuropeptides in the innervation of the submandibular gland and in the ganglionic cells of the submandibular ganglion was examined ten days and six months after treatment. Antisera directed against enkephalin and bombesin and immunohistochemical methods were used. The effects of bilateral irradiation on the staining pattern of various neuropeptides in the cervical spinal cord were also studied. In the submandibular gland and in the submandibular ganglionic cells, there was a markedly increased neuropeptide expression ten days after bilateral treatment, as seen after staining with both antisera used, while no changes occurred after unilateral treatment. Six months after treatment, the pattern of neuropeptide expression in the submandibular gland/ganglion corresponded to that seen in controls. Irradiation did not lead to any changes in the staining pattern of neuropeptides in the spinal cord. The observations show that there is a great complexity in the susceptibility of nervous tissues to radiotherapy with respect to influences on the expression of neuropeptides.

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“…Moreover, sublethal damage following fractionated irradiation seems to cause alterations in cell membrane function and in physiological parameters (Reade & Steidler, 1985; Stephens et al, 1986a,b;Franzen et al, 1991). Most recently, it was also demonstrated that irradiation enhances the expression of important neutopeptides/growth factors, at least in salivary glands (Forsgren et al, 1992;Franzen et al, 1993). Furthermore, parotid acinar cell death following irradiation has been described as an interphase death (Stephens et al, 1986a,b;Franzen et al, 1991).…”

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confidence: 99%

Increase in mast cells and hyaluronic acid correlates to radiation-induced damage and loss of serous acinar cells in salivary glands: the parotid and submandibular glands differ in radiation sensitivity

Henriksson

Frojd²,

Gustafsson³

et al. 1994

Br J Cancer

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Summary The detailed mechanisms which can explain the inherent radiosensitivity of salivary glands remain to be elucidated. Although DNA is the most plausible critical target for the lethal effects of irradiation, interactions with other constituents, such as cell membrane and neuropeptides, have been suggested to cause important physiological changes. Moreover, mast cells seem to be closely linked to radiation-induced pneumonitis. Therefore, in the present study the effects of fractionated irradiation on salivary glands have been assessed with special regard to the appearance of mast cells and its correlation with damage to gland parenchyma. Sprague-Dawley strain rats were unilaterally irradiated to the head and neck with the salivary glands within the radiation field. Although the detailed mechanisms by which radiation induces damage in biological tissues are not fully understood, it is generally accepted that generation of free radicals is of major importance. DNA is the most likely target for the lethal effects of these irradiation induced free radicals, however it is plausible that other compartments, i.e. non-genetic macromolecules, such as proteins and carbohydrates, can be significantly affected with vital alterations in the functional integrity of the certain biological tissues (Creasy, 1960;Desai et al., 1964;Sutherland et al., 1967;Alper, 1977;El-Mofty et al., 1981;Franzen et al., 1991;1993). In addition, changes caused by external factors and in the surrounding tissues can play an important role in modifying the final detectable and evaluable reaction, which indeed has recently been proposed, e.g. ongoing smoking depressed pneumonitis caused by irradiation in humans (Franzen et al., 1989;Bjermer et al., 1990; as well as in experimental animals . Moreover, sublethal damage following fractionated irradiation seems to cause alterations in cell membrane function and in physiological parameters (Reade & Steidler, 1985; Stephens et al., 1986a,b;Franzen et al., 1991). Most recently, it was also demonstrated that irradiation enhances the expression of important neutopeptides/growth factors, at least in salivary glands (Forsgren et al., 1992;Franzen et al., 1993). Furthermore, parotid acinar cell death following irradiation has been described as an interphase death (Stephens et al., 1986a,b;Franzen et al., 1991).The remarkable sensitivity of salivary gland acinar cells compared with other glands to radiation is a unique radiobiological phenomenon (Shannon et al., 1978;Mira et al., 1982;Abok et al., 1984;Junglee et al., 1986;Franzen et al., 1991). Other well-differentiated gland cells are known to be more or less radioresistant (Rubin & Casarett, 1972). The exact mechanism which explains this sensitivity is not entirely understood. Since mast cells have been proposed to interact in a substantial manner with the development of radiationinduced pneumonitis and pulmonary fibrosis (Franzen et al., 1989;Bjermer et al., 1990; Nilsson et al., 1990a,b; we found it of interest to evaluate the correlation of connecti...

show abstract

Bilateral irradiation of head and neck induces an enhanced expression of substance p in the parasympathetic innervation of the submandibular gland

Cited by 28 publications

References 29 publications

Distribution of neuropeptide-containing nerve fibers in the human submandibular gland, with special reference to the difference between serous and mucous acini

Distribution of neuropeptide-containing nerve fibers in the human submandibular gland, with special reference to the difference between serous and mucous acini

Effects of irradiation on neuropeptide expression in rat salivary gland and spinal cord

Increase in mast cells and hyaluronic acid correlates to radiation-induced damage and loss of serous acinar cells in salivary glands: the parotid and submandibular glands differ in radiation sensitivity

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