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K Ono

Publications and source records attributed to K Ono.

At least 559 records · Page 31Linked to original sources

Endothelin-A receptor mediates cardiac inhibition by regulating calcium and potassium currents.

Voltage-sensitive ion channels play fundamental roles in the regulation of cardiac function by various neurotransmitters. Endothelins have strong positive inotropic and chronotropic effects, for which recent studies have implicated various intracellular mechanisms. However, very little is known about the underlying ion-channel regulation by the peptide. We report here that endothelin-1 consistently hyperpolarizes the membrane and shortens the duration of the action potential in mammalian atrial myocytes, leading to suppression of electrical excitability of the heart. Endothelin-1, but not endothelin-3, inhibited the L-type calcium current by decreasing cyclic AMP accumulation and activated the muscarinic potassium current by stimulating a pertussis toxin-sensitive GTP-binding protein. Consistent with these results, endothelin-1 strongly reduced the heart rate when it was increased by beta-adrenoceptor stimulation. These effects were blocked by an ETA (endothelin-1-selective) receptor-selective antagonist, BQ123 (refs 8-11). The ETA receptor-mediated regulation of cardiac ion channels gives new insight into our understanding of the physiological and pathophysiological roles of endothelins in the control of cardiac function.

Action Potentials↗

A staging system for soft-tissue sarcoma and its evaluation in relation to treatment.

In order to define the significant factors for a staging system of soft-tissue sarcomas (STS), histologic and clinical findings in 190 adult patients with localized STS in the extremities and trunk were reviewed. The male-to-female ratio was 1.21. The histologic grading of tumors was defined according to the criteria recently proposed by us: tumors were low-grade in 65 cases, intermediate-grade in 57 cases and high-grade in 68 cases. The initial surgical procedure was as follows: intracapsular excision in 9 cases, marginal excision in 104 and wide local excision in 77, including 15 amputations. The mode of treatment was surgery alone (101 patients), surgery and chemotherapy (58), surgery and radiotherapy (22) and surgery and combined chemo- and radiotherapy (9). Univariate analysis revealed histologic grade, sex, tumor size and tumor depth to be significant prognostic factors. Multivariate analysis revealed histologic grade to be the only independent factor for prognosis. Significant clinical factors in each histologic grade were then evaluated. In the low-grade group, local recurrence significantly affected prognosis. Most of the patients with local recurrence had had marginal resection as the initial surgical procedure. No clinical factors affecting prognosis in the intermediate-grade group could be determined. In the high-grade group, patients with wide local excision and adjuvant chemotherapy had a better prognosis than those with marginal excision with or without adjuvant chemotherapy and wide local excision without chemotherapy (p = 0.09). In conclusion, histologic grade was the only significant factor for the staging of STS. On the basis of our staging system, different modalities of treatment for each grade of STS might be indicated; adequate surgery is essential for the prevention of local recurrence, which resulted in reduced mortality in patients with low-grade STS. For high-grade STS, the prevention of distant metastasis by combined extensive surgery and adjuvant chemotherapy may make long-term survival possible.

Adult↗

Cation-dependent gating of the hyperpolarization-activated cation current in the rabbit sino-atrial node cells.

1. The gating properties of the hyperpolarization-activated cation current (I(f) or Ih) were investigated in single pacemaker cells dissociated from the rabbit sino-atrial node. 2. The whole-cell I(f) was recorded in the presence of different external cations. The inward I(f) was increased when external Na+ was replaced with K+, and was decreased in Li+ or Rb+ solution. In Tris+ and Cs+ solutions, the inward I(f) was negligible. The outward tail current recorded upon depolarization was largest in Li+ solution and smaller in a sequence of Na+, Tris+ and K+ solutions. In Rb+ and Cs+ solutions, only a small tail current was recorded. 3. The outward tail current had a 'shoulder' in Na+ solution, which was much delayed by replacing Na+ with Li+. In K+ solution, the decay of the tail current was much faster, and no obvious shoulder was recorded. The tail current was slowest in Li(+)-rich and 0 mM K+ solution, and was progressively accelerated by adding K+ over the range from 0 to 3 mM. The tail current at 30 mM [K+]o showed only a small shoulder. A common binding site to modulate the I(f) deactivation was suggested for monovalent cations. 4. The shoulder of the I(f) tail became more evident as I(f) was activated to a larger extent either by prolonging the duration or by increasing the amplitude of the preceding hyperpolarization in both Na+ and Li+ solutions. 5. The I(f) was first activated by hyperpolarizing the membrane to -110 mV, and then deactivated by depolarization. The inward tail current at -50 mV showed a single exponential decay. At more positive potentials, the shoulder of the outward tail currents became more evident and the rate of the final decay was increased. 6. The time course of I(f) activation was well fitted with the sum of two exponential functions. Time constants of both components were not affected by the external cation (Na+, K+ or Li+) replacement. Likewise, the quasi-steady state activation was conserved when external Na+ was replaced with Li+. 7. Two closed and three open states were assumed in a sequential state model of the I(f) channel. The cation effects were well simulated by assuming that the deactivation rate was selectively modulated. The flow of I(f) during the spontaneous action potential was calculated. The activation of I(f) started on repolarization to the maximum diastolic potential and reached a maximum in the middle of the diastolic period. Its peak amplitude was 14% of the net inward current during the diastolic period.

Animals↗

The radiosensitivity of quiescent cell populations in murine solid tumors in irradiation with fast neutrons.

PURPOSE: We analyzed the characteristics of radiosensitivity and potentially lethal damage repair in the quiescent cell populations of murine SCC VII solid tumors irradiated with fast neutrons, in comparison with those irradiated with 10 MV X rays. METHODS AND MATERIALS: SCC VII tumor-bearing C3H/He mice were irradiated with 30 MeV fast neutrons or 10 MV X rays after receiving 10 injections of 5-bromo-2'-deoxyuridine (BUdR) to label all proliferating tumor cells. Immediately or 24 h after irradiation, the tumors were excised and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus frequency in cells without BUdR labeling was determined using immunofluorescence staining to BUdR. This micronucleus frequency was then used to calculate the surviving fraction of unlabeled cells from the regression line for the relation between micronucleus frequency and the surviving fraction of all tumor cells. Thus, a cell survival curve could be determined for the cells not labeled by BUdR, which can be regarded as the quiescent cells for all practical purposes. RESULTS: The difference in intrinsic radiosensitivity between all tumor and quiescent cells became smaller by using fast neutrons, compared with X rays, especially when large radiation doses were given. Potentially lethal damage repair by quiescent cells was less evident following irradiation with fast neutrons than with X rays, especially when large doses were delivered. CONCLUSION: By using fast neutrons in clinical radiotherapy, the radiosensitivity of solid tumors is thought to depend on their heterogeneity less critically than for X rays.

Animals↗

Middle dose rate irradiation in combination with carbogen inhalation selectively and more markedly increases the responses of SCCVII tumors.

PURPOSE: Carbogen increases the radiation response of tumors and reduced dose rate irradiation spares the damage of normal tissues. The purpose in this paper is to investigate the possibility of selective radiosensitization of tumors by reduced dose rate irradiation in combination with carbogen inhalation. METHODS AND MATERIALS: SCCVII tumors in C3H/He mice were irradiated at middle dose rate (0.1 Gy/min) or high dose rate irradiation (3.0 Gy/min) in combination with carbogen inhalation. The mice were enclosed in a box with carbogen flushing at 1.01/min. The tumor response was measured by a cytokinesis block micronucleus assay. The effects on intestinal crypt cells and bone marrow cells were investigated by microcolony assay or Hendry's method, respectively. RESULTS: The anti-tumor effect of middle dose rate irradiation was equal to that of a high dose rate irradiation. Carbogen inhalation, more efficiently, increased the antitumor effect when combined with middle and high dose rate irradiation, and yielded enhancement ratios of 1.6 at around 2 Gy. Middle dose rate irradiation produced less damage on intestinal crypt cells and bone marrow cells in comparison with high dose rate irradiation, and carbogen inhalation never enhanced the responses of these normal tissues in combination with middle dose rate irradiation. Dose modifying factors were 1.3-2.0. CONCLUSION: Since middle dose rate irradiation in combination with carbogen inhalation gave the therapeutic gain factors of 2.0-3.2, which were much larger than those obtained with any other radiosensitizers, this combination has a potential as a new modality for improving the results of cancer radiotherapy.

Animals↗

Background conductance attributable to spontaneous opening of muscarinic K+ channels in rabbit sino-atrial node cells.

Single myocytes were dissociated from the rabbit sino-atrial node, and the membrane background conductance produced by spontaneous opening of the muscarinic K+ channels was investigated by recording whole-cell and single channel currents in both normal K+ (5.4 mM) and high-K+ (145 mM) external solutions. Increasing external K+ concentration ([K+]o) from 5.4 to 145 mM induced a large inward shift of the whole-cell current accompanied by considerable current fluctuations at -50 mV. The high-K(+)-induced current was both K+ selective and voltage dependent, which was examined by varying [K+]o. This current was almost completely suppressed by 1-5 mM Ba2+ or 2-10 mM Cs+ and it was partly blocked by 10 microM atropine. In high-K+ (145 mM) solution, 20 nM acetylcholine (ACh) further increased the K+ conductance as well as the current noise. The power density spectrum of the noise was fitted with a sum of two Lorentzian functions. The corner frequencies of both the slow (approximately 5 Hz) and fast (approximately 120 Hz) components were comparable between the noise before and during the ACh application. Internal dialysis with a non-hydrolysable derivative of ATP, 5'-adenylylimido-diphosphate (AMP-PNP) or Mg(2+)-free solution markedly decreased both the amplitude and fluctuations of the high-K(+)-induced current. The relation between the variance of the current fluctuations and the mean current amplitude was linear in every experiment using dialysis of AMP-PNP or Mg(2+)-free internal solution, or using superfusion of ACh. The slopes of these relations gave comparable single channel current amplitudes of -0.7 pA at -50 mV. These results indicate that the spontaneous opening of the muscarinic K+ channels is largely responsible for the high-K(+)-induced current. In the high-K+ solution, the variance-mean relation at -50 mV showed that the muscarinic K+ channel provides an inward current of 3.12 +/- 2.13 pA pF-1 (n = 23), which was about 60% of the total inward background current. In the normal K+ solution, the variance-mean relation at -50 mV indicated that an outward current of 6.0 +/- 2.0 pA (0.33 +/- 0.28 pA pF-1, n = 8) was provided by the K+ channel. The single channel current amplitude was estimated to be 0.06 +/- 0.02 pA (n = 9). Cell-attached recordings in the absence of ACh demonstrated sporadic and brief openings of channels identical to the ACh-induced channels. The power density spectra of the single channel currents exhibited kinetic properties comparable with those of the whole-cell currents.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

Limited diffusibility of gene products directed by a single nucleus in the cytoplasm of multinucleated myofibres.

Two types of beta-galactosidase genes, whose products are distributed in the nucleus (N beta-gal) or cytoplasm (C beta-gal), were injected with fructose intramuscularly into the quadriceps of adult mice. Regionally restricted and overlapped distributions of both gene products were observed in the myofibres. These findings indicate that N beta-gal is incorporated into the nucleus responsible for its synthesis and that C beta-gal becomes located in the vicinity of the nucleus after its synthesis. This restricted location of C beta-gal in myofibres remained unchanged during the development of infant mouse muscle. Thus, the gene products directed by the nucleus of myofibres seem to show limited diffusibility, suggesting a universal localization of subcellular domains in myofibres.

Animals↗

Transient and localized expression of bone morphogenetic protein 4 messenger RNA during fracture healing.

Temporal and spatial distribution of a gene encoding murine bone morphogenetic protein 4 (mBMP-4) during fracture repair were investigated in mice by RT-PCR and in situ hybridization. For in situ hybridization, fractured ribs and surrounding tissues were decalcified and hybridized with a mBMP-4-specific complementary RNA probe labeled with digoxigenin-11 UTP. mBMP-4 messenger RNA (mRNA) was not detected in ribs without fracture, whereas it was detected only in the early phase of fracture from 12 to 72 h after the onset of fracture before new cartilage or bone formation. The mBMP-4 mRNAs were present in cells distributed in three distinct regions, namely, the proliferating periosteum, the medullary cavity, and the muscles near the fracture site. These BMP-4-positive cells did not express bone gla protein mRNA, which is a marker of the mature osteogenic cell. RT-PCR also showed a transient increase in the level of BMP-4 mRNA in the early phase of fracture repair. The findings provide us with some new information. (1) The BMP-4 gene is produced by less differentiated osteoprogenitor cells, not by differentiated osteoblasts. (2) The BMP-4 gene is enhanced by the impact of fracture and localized in callus-forming tissue before callus formation. Together with the activities of BMP-4, as was previously described, our results suggest that newly produced BMP-4 gene product is one of the local contributing factors in callus formation in the early phase of fracture healing.

Animals↗

Bone morphogenetic protein 2 stimulates osteogenesis but does not affect chondrogenesis in osteochondrogenic differentiation of periosteum-derived cells.

The effects of recombinant human bone morphogenetic protein 2 (rhBMP-2) on osteochondrogenesis were examined in high-density cultures of periosteum-derived cells, which have the potential to differentiate into bone and hypertrophic cartilage in vitro. Proliferation of these cells was inhibited by treatment with rhBMP-2. The time course for alkaline phosphatase (ALP) expression was shortened and the mineralization of the culture was increased by supplementation with rhBMP-2. These stimulatory effects of rhBMP-2 were observed at doses of 10-100 ng/m. Bone Gla protein (BGP) was immunocytochemically detectable earlier in the culture treated with rhBMP-2, and the BGP-positive layer of the rhBMP-2-treated cultures was thicker than that of the control cultures. On the other hand, there was no difference in uronic acid content or the time course of alpha 1(II) collagen mRNA expression between the rhBMP-2-treated and the control cultures. These results indicate that rhBMP-2 shortens the time course of osteogenesis and increases the amount of bone formation, whereas chondrogenesis remains unaffected.

Alkaline Phosphatase↗

Effect of tumor suppressors on cell cycle-regulatory genes: RB suppresses p34cdc2 expression and normal p53 suppresses cyclin A expression.

We show that expression of the p34cdc2 and cyclin A genes is induced by interleukin-2 in normal human T cells and present evidence to support the idea that these genes are deregulated in leukemic T cells. Our DNA sequencing data indicate that the promoter region of the p34cdc2 gene contains putative E2F-like binding sites which are recognized by Rb and binding sites for c-myb, Sp1, and ATF, and that the promoter region of the cyclin A gene contains binding sites for p53, Sp1, and ATF. In this study we focus on the effect of p53 and Rb on these cell cycle-regulatory genes. Cotransfection of Y79 human retinoblastoma cells with a p34cdc2 promoter-luciferase expression vector and a plasmid expressing the retinoblastoma gene (RB) indicated that RB suppresses p34cdc2 expression. Cotransfection of B104 rat neuroblastoma cells with a cyclin A promoter-luciferase expression vector and a plasmid expressing the normal or mutant p53 indicated that only the normal p53 suppresses cyclin A expression. In normal T cells, PHA stimulation reduces the amount of complexes in the p34cdc2 promoter between the E2F-like binding site and the RB gene product. These complexes were not detected in leukemic T cells. Our data support the idea that tumor suppressors modulate the expression of cell cycle-regulatory genes: RB regulates p34cdc2 expression and p53 regulates cyclin A expression.

Base Sequence↗

Postnatal development of neuropeptide Y- and calcitonin gene-related peptide-immunoreactive nerves in the rat urinary bladder.

The postnatal development of neuropeptide Y- and calcitonin gene-related peptide-immunoreactive (NPY-IR and CGRP-IR) nerve fibers in the rat urinary bladder was investigated using whole-mount preparations and cryostat sections. In newborn and 3-day-old rats, many NPY-IR nerve fibers were observed in the subserous and muscle layers. Many NPY-IR nerve cell bodies clustered at branching points of the subserous nerve bundles. Within 4 weeks after birth, these cell bodies drastically decreased in number and spread along the bundles, although the number of NPY-IR nerve fibers increased moderately. In contrast, CGRP-IR nerve fibers in newborn and 3-day-old rats were less developed, and no CGRP-IR nerve cell body was observed in any rat. However, CGRP-IR nerve fiber distribution in the urinary tissues conspicuously increased within 4 weeks after birth. Especially, an increase of the infraepithelial fibers showing a meshwork appearance was prominent in the fundus and corpus of the bladder. The infra- and intraepithelial CGRP-IR nerve meshwork of the ventral wall was more dense than that of the trigone. At 4 weeks, NPY-IR and CGRP-IR nerves were similar to those of the adult rat (8-12 weeks old). The present study suggests a correlation between the development of the peripheral nervous system in the urinary bladder and maturation of micturition behavior in the rat.

Animals↗

Configuration of myoepithelial cells in various exocrine glands of guinea pigs.

To study the configuration of myoepithelial cells, we isolated glandular endpieces of various guinea pig glands by collagenase, and visualized the myoepithelial cells by immunohistochemistry for actin, or by Bodipy-phallacidin, under both a light microscope and laser scanning confocal microscopes. In parotid and mandibular glands, the glandular acini were small (about 20-30 microns diameter) and spherical, and each acinus had one or two myoepithelial cells attached that were stellate in shape (central cell body and four to six thin processes). Most of the basal surface of the glandular cells was not covered by myoepithelial cells, and processes often extended to the neighboring acinus. The tubular glandular endpieces of the major sublingual gland, which secretes a mucous substance, were almost fully encircled by band-like myoepithelial cells (about 3-6 microns wide). Although there were many differences between the lacrimal gland and the Harderian gland (e.g., the secretory product of the lacrimal gland was mucous, and glandular lumina were narrow; the Harderian gland secreted lipids and showed wide lumina), the outer contours of both glandular endpieces were the same (about 50-100 microns diameter, ellipsoid or spherical in shape). In both glands, 5-20 stellate myoepithelial cells were attached onto a glandular endpiece, and their arrangement had a lacy appearance. Actin filaments in myoepithelial cells aggregated and formed bundles in the broad processes and cell bodies. The bundles ran across the cell body, but there was no point where the bundles converged. In the arborization, some distal processes reversed their direction. We conclude that the configuration of myoepithelial cells depends on the outer contour of the glandular endpieces rather than on the secretory material or luminal width. The variety of myoepithelial cell configurations in the different exocrine glands we examined suggests that it is quite difficult to assign to myoepithelial cells the general role of expelling secretory products from glandular lumina. These cells seem to maintain the contour of the glandular endpieces, serving as the exoskeleton of the endpieces.

Animals↗

Immunocytochemical study of tyrosine hydroxylase and dopamine beta-hydroxylase immunoreactivities in the rat pancreas.

An immunohistochemical and immunoelectron microscopic study was used to demonstrate tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) immunoreactivities in the rat pancreas. Small TH immunoreactive cells were found in close contact with large TH immunonegative ganglion cells among the exocrine glands and were occasionally found in some islets. Some of these TH immunoreactive cells were also DBH immunopositive. The immunoreaction product was seen diffusely in the cytoplasm and in the granule cores of TH immunoreactive cells. All intra-pancreatic ganglion cells were immunoreactive for DBH, but not for TH. The TH immunoreactive cells were identified as small intensely fluorescent (SIF) cells due to their localization and morphological characteristics and showed no insulin, glucagon, somatostatin or pancreatic polypeptide immunoreactivities. These results indicate that SIF cells may release dopamine or noradrenaline to adequate stimuli while the intra-pancreatic ganglion cells with only DBH may not synthesize catecholamines in a normal biosynthetic pathway. TH immunoreactive nerve bundles without varicosities and fibers with varicosities, associated or unassociated with blood vessels, were found in both the exocrine and endocrine pancreas. Close apposition of TH immunoreactive nerve fibers to the smooth muscle and endothelial cells of the blood vessels was observed. A close apposition between TH immunoreactive nerve fibers and exocrine acinar cells and islet endocrine cells was sometimes found in the pancreas. The immunoreaction product was seen diffusely in the axoplasm and in the granular vesicles of the immunoreactive nerve fibers. Since no TH immunoreactive ganglion cells were present in the rat pancreas, the present study suggests that noradrenergic nerve fibers in the pancreas may be extrinsic in origin, and may exert an effect on the regulation of blood flow and on the secretory activity of the acinar cells, duct cells and endocrine cells.

Animals↗

Ganglion cells immunoreactive for catecholamine-synthesizing enzymes, neuropeptide Y and vasoactive intestinal polypeptide in the rat adrenal gland.

Immunohistochemistry has been used to demonstrate tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) immunoreactivities, and acetylcholinesterase (AChE) activity was demonstrated in rat adrenal glands. The TH, DBH, NPY and VIP immunoreactivities and AChE activity were observed in both the large ganglion cells and the small chromaffin cells whereas PNMT immunoreactivity was found only in chromaffin cells, and not in ganglion cells. Most intra-adrenal ganglion cells showed NPY immunoreactivity and a few were VIP immunoreactive. Numerous NPY-immunoreactive ganglion cells were also immunoreactive for TH and DBH; these cells were localized as single cells or groups of several cells in the adrenal cortex and medulla. Use of serial sections, or double and triple staining techniques, showed that all TH- and DBH-immunoreactive ganglion cells also showed NPY immunoreactivity, whereas some NPY-immunoreactive ganglion cells were TH and DBH immunonegative. NPY-immunoreactive ganglion cells showed no VIP immunoreactivity. AChE activity was seen in VIP-immunopositive and VIP-immunonegative ganglion cells. These results suggest that ganglion cells containing noradrenaline and NPY, or NPY only, or VIP and acetylcholine occur in the rat adrenal gland; they may project within the adrenal gland or to other target organs. TH, DBH, NPY, and VIP were colocalized in numerous immunoreactive nerve fibres, which were distributed in the superficial adrenal cortex, while TH-, DBH- and NPY-immunoreactive ganglion cells and nerve fibres were different from VIP-immunoreactive ganglion cells and nerve fibres in the medulla. This suggests that the immunoreactive nerve fibres in the superficial cortex may be mainly extrinsic in origin and may be different from those in the medulla.

Adrenal Glands↗

Voltage- and time-dependent block of I(f) by Sr2+ in rabbit sino-atrial node cells.

The hyperpolarization-activated cation current (I(f)) was recorded in single myocytes dissociated from the rabbit sino-atrial node and the Sr(2+)-mediated block of I(f) examined. In the presence of 0.1-10 mM Sr2+, the activation phase of I(f) was followed by a slower decay during hyperpolarization. In the steady state I/V diagram, the Sr2+ block progressed with increasing hyperpolarization. Ba2+ also blocked I(f), but no time dependency could be observed. The blocking effect of Ca2+ was weak, and Mg2+ had little effect on I(f). The relationship between extracellular Sr2+ concentration [Sr2+]o and the block was described by a Hill coefficient of 1. The half-saturating [Sr2+]o were 2.0, 1.6, 1.1 and 0.65 mM at -90, -100, -110 and -120 mV, respectively. The rapid application of Sr2+ during the full activation of I(f) using the jet-stream method induced an exponential decline of I(f). The reciprocal time constants were linearly correlated to [Sr2+]o, suggesting 1:1 binding stoichiometry. The fractional electrical distance for the binding site was approximately 0.5 from the external side of the channel. Based on the multiple closed and open states for the I(f) channel, a mathematical model for the Sr2+ block was constructed in which the time course of I(f) in the presence of Sr2+ was described by the sum of three exponential functions. Fitting the model to the original traces revealed blocking and unblocking rates similar to those obtained from the jet-stream method. At -110 mV, the blocking rate was 410 M-1 s-1 while the unblocking rate was 0.16 s-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunohistochemical and histochemical evidence for the presence of noradrenaline, serotonin and gamma-aminobutyric acid in chief cells of the mouse carotid body.

The immunohistochemical study revealed tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), serotonin, glutamate decarboxylase (GAD) and gamma-aminobutyric acid (GABA) immunoreactivities in the mouse carotid body. TH and DBH immunoreactivities were found in almost all chief cells and a few ganglion cells, and in relatively numerous varicose nerve fibers of the carotid body. The histofluorescence microscopy showed catecholamine fluorescence in almost all chief cells. However, no PNMT immunoreactivity was observed in the carotid body. Serotonin, GAD and GABA immunoreactivities were also seen in almost all chief cells of the carotid body. From combined immunohistochemistry and fluorescence histochemistry, catecholamine and serotonin or catecholamine and GABA were colocalized in almost all chief cells. Thus, these findings suggest that noradrenaline, serotonin and GABA may be synthesized and co-exist in almost all chief cells of the mouse carotid body and may play roles in chemoreceptive functions.

Animals↗