Circulating CGRP comes from the perivascular nerves.
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Animals↗
Biomedical subjects
I MacIntyre
Publications and source records attributed to I MacIntyre.
Light and electron microscopic studies of calcitonin gene-related peptide-like immunoreactive neurons and axon terminals of the nucleus of the tractus solitarius of the rat.
This study was an examination of the ultrastructural characteristic features of calcitonin gene-related peptide (CGRP)-like immunoreactive neurons and their axon terminals in the nucleus of the tractus solitarius of the rat. Some axon terminals were identified as receiving synaptic inputs from non-immunoreactive axon terminals. This may suggest that part, if not all, CGRP containing afferents are affected presynaptically by other afferents.
Animals↗
The calcitonin gene-related peptide-containing fiber projection from the hypothalamus to the lateral septal area including its fine structures.
The afferent source of calcitonin gene-related peptide-like immunoreactive (CGRPI) fibers in the lateral septal area of the rat was sought by using indirect immunofluorescence technique. These fibers decreased markedly on the operated side after the destruction of the area between the anterior hypothalamic nucleus and the lateral hypothalamus where there were a number of CGRPI cells. We also examined the fine structure of CGRPI fibers in the lateral septal area. Many CGRPI fibers forming axosomatic synapses were identified. These facts strongly suggest that CGRPI cells in the area between the anterior hypothalamic nucleus and the lateral hypothalamus project ipsilaterally to the lateral septal area and directly influence the soma there.
Animals↗
Calcitonin gene-related peptide projection from the ventromedial thalamic nucleus to the insular cortex: a combined retrograde transport and immunocytochemical study.
We employed a highly sensitive combination method of retrograde tracing and immunohistochemistry to identify calcitonin gene-related peptide (CGRP)-containing fiber pathways in the rat from the ventrolateral part of the ventrolateral thalamic nucleus (vl-vl) and the caudal continuation to the insular cortex. Biotin-wheat germ agglutinin (B-WGA) injected into the insular cortex labeled numerous neurons in the vl-vl and the caudal continuation ipsilaterally; simultaneous staining with CGRP antiserum revealed that some of these neurons are CGRP positive.
Animals↗
Effect of calcitonin gene-related peptide on contraction of striated muscle in the mouse.
We have found ultrastructurally calcitonin gene-related peptide-like immunoreactivity in the axon terminal within the synaptic trough of neuromuscular junction of the mouse. We determined, using pharmacological means, with a phrenic nerve-diaphragm preparation, that this peptide enhances muscle contraction during stimulation of the nerve fibers or direct stimulation of the muscle. This effect is probably brought about via the receptor for this peptide not the acetylcholine receptor.
Animals↗
Prevention of postmenopausal osteoporosis.
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Calcium↗
Calcitonin gene-related peptide: potent vasodilator and major product of calcitonin gene.
In addition to calcitonin and katacalcin, the human calcitonin gene encodes a novel peptide--calcitonin gene-related peptide (CGRP)--a potent vasodilator. A sensitive and specific radioimmunoassay was developed to study plasma levels of CGRP in normal subjects. CGRP circulates at five times the concentration of calcitonin, suggesting that it may be an important physiological regulator of vascular tone and blood flow.
Adult↗
Co-localization of calcitonin gene-related peptide-like immunoreactivity with substance P in cutaneous, vascular and visceral sensory neurons of guinea pigs.
Calcitonin gene-related peptide (CGRP) has been immunohistochemically co-localized with substance P (SP) in capsaicin-sensitive, varicose axons supplying the skin, viscera and cardiovascular system of the guinea pig. After treatment with colchicine in vitro, 82% of SP neurons in the dorsal root ganglia contained CGRP-like immunoreactivity while 96% of CGRP neurons were immunoreactive for SP. Both CGRP- and SP-like immunoreactive material are transported peripherally and centrally from dorsal root ganglia. Thus, in tissues such as the gut where there are intrinsic nerves containing SP but lacking CGRP, CGRP-like immunoreactivity is a useful means of specifically labelling axons of most sensory neurons containing SP.
Animals↗
Coexistence of calcitonin gene-related peptide and substance P-like peptide in single cells of the trigeminal ganglion of the rat: immunohistochemical analysis.
The localization of calcitonin gene-related peptide (CGRP) and substance P (SP) in the rat trigeminal ganglion was examined by means of the indirect immunofluorescent method. About 40% of neurons in the ganglion contained CGRP-like immunoreactivity (CGRPI), while about 20% of neurons showed SP-like immunoreactivity (SPI). In serial sections, nearly all the SPI neurons contained CGRPI.
Animals↗
Immunohistochemical evidence for the coexistence of calcitonin gene-related peptide- and choline acetyltransferase-like immunoreactivity in neurons of the rat hypoglossal, facial and ambiguus nuclei.
The present immunocytochemical study demonstrates that calcitonin gene-related peptide-like immunoreactivity (CGRPI) coexists with acetylcholine in single cells of hypoglossal, facial and ambiguus nuclei. The experiments were done using alternate frozen sections from relevant regions of the rat brain. We further show that CGRPI is localized in the nerve terminals that form neuromuscular junctions in the tongue muscles.
Animals↗
Occurrence of calcitonin gene-related peptide in the chicken amacrine cells.
The distribution of calcitonin gene-related peptide (CGRP)-like immunoreactivity (CGRPI) in the chicken retina was investigated by means of immunohistochemistry. CGRPI was localized in the stratified amacrine cells. The terminal branching pattern of these cells was different between the central and peripheral retinal regions. Flat-mount preparations revealed these CGRPI cells to be evenly distributed in the entire retina with surprisingly rich arborization.
Animals↗
Topographic localization of calcitonin gene-related peptide in the rat brain: an immunohistochemical analysis.
The distribution of immunoreactive calcitonin gene-related peptide in the rat brain was investigated by means of an indirect immunofluorescence method. In addition to previously reported calcitonin gene-related peptide-like immunoreactive structure-containing sites such as the nucleus ambiguus, nucleus originis nervi facialis, nucleus originis nervi hypoglossi, nucleus peripeduncularis and nucleus parabrachialis, the present study demonstrated a far wider distribution of calcitonin gene-related peptide-like immunoreactive structure-containing cells in the rat brain, i.e. the nucleus hypothalamicus lateralis, nucleus ventromedialis thalami, colliculus superior, lemniscus lateralis, gyrus dentatus, nucleus olivaris superior, nucleus tractus solitarii, nucleus cuneiformis, nucleus parabigeminalis and a proportion of the Purkinje cells. We have also demonstrated a more extensive network of calcitonin gene-related peptide-like immunoreactive fibers distributed in various areas throughout the rat brain than has been reported previously such as the colliculus inferior, nucleus olivaris superior, nucleus vestibularis lateralis and inferioris, and nucleus cochlearis dorsalis and ventralis, etc.
Animals↗
Calcitonin gene-related peptidergic projection from the parabrachial area to the forebrain and diencephalon in the rat: an immunohistochemical analysis.
We investigated ascending fiber projections of calcitonin gene-related peptide from the parabrachial area to the forebrain and diencephalon in the rat using immunocytochemistry. Destruction of the lateral portion of the dorsal parabrachial area resulted in a marked ipsilateral decrease in the fibers containing calcitonin gene-related peptide in the ventromedial hypothalamic nucleus, indicating that cells containing calcitonin gene-related peptide in the lateral portion of the dorsal parabrachial area projected to the ipsilateral ventromedial hypothalamic nucleus. Destruction of the ventral portion of the parabrachial area resulted in a marked decrease of fibers containing calcitonin gene-related peptide in the bed nucleus of the stria terminalis, the central amygdaloid nucleus and the lateral hypothalamus just medial to the crus cerebri (the far-lateral hypothalamus), and a less marked decrease in the ventromedial thalamic nucleus. This means that there are projections from cells containing calcitonin gene-related peptide in the ventral portion of the parabrachial area to the first three regions just mentioned, and to some extent to the last.
Afferent Pathways↗
Distribution of calcitonin gene-related peptide in the rat peripheral nervous system with reference to its coexistence with substance P.
This immunocytochemical study, using a double-staining method, showed that calcitonin gene-related peptide-like immunoreactive structures are widely distributed in the peripheral nervous system and that many of them coexist with substance P-like immunoreactive structures in single sensory ganglion cells. Neurons positive for calcitonin gene-related peptide but negative for substance P were detected in sensory ganglia. These cells were large (about 30-45 micron in diameter); these primary sensory neurons containing calcitonin gene-related peptide can probably act independently of substance P. There were neurons containing calcitonin gene-related peptide without substance P in the pterygopalatine ganglion, although these cells were less numerous than in the sensory ganglia. In consecutive sections, calcitonin gene-related peptide-like structures occurred in thyroid parafollicular cells, which also contain calcitonin. This suggested that messenger RNA for producing calcitonin gene-related peptide is also present in the thyroid, and like calcitonin, calcitonin gene-related peptide may have a peripheral physiological role.
Animals↗
Specific binding of 1,25 dihydroxyvitamin D3 in lymphocytes.
We examined ten cellular or tissue sources of lymphocytes for specific binding of 1,25(OH)2D3, the hormonally active form of vitamin D3. A specific-binding protein was found in three of these sources. Scatchard analysis of cytosol from a follicular lymphoma cell line revealed binding sites with a Kd of 7.0 X 10(-11) and a receptor concentration of 6.6 fmol/mg protein. Sucrose density centrifugation of 3H-1,25(OH)2D3 labeled cytosol showed a 3.75 peak which was absent in cytosols incubated with excess nonradioactive 1,25(OH)2D3. The relative amounts of vitamin D3 metabolites required to displace 50% of the specifically bound 3H-1,25(OH)2D3 were 1,25(OH)2D3: 1,24,25(OH)3D3: 25(OH)D3: 24,25(OH)2D3 = 1: 180: 1000: 2700. Excess vitamin D3, cortisol, and estradiol failed to displace 3H-1,25(OH)2D3. Scatchard analysis of spleen cytosol from a patient with prolymphocytic transformation of chronic lymphocytic leukemia demonstrated a binding protein with a Kd of 1.2 X 10(-10) and a receptor concentration of 0.2 fmol/mg protein. DNA cellulose binding confirmed the presence of the specific-binding protein in this cytosol. Specific binding of 3H-1,25(OH)2D3 was also quantitated in a cell line from a patient with Burkitt's lymphoma with a Kd of 0.3 X 10(-10) and a receptor concentration of 29.6 fmol/mg protein. No specific binding of 3H-1,25(OH)2D3 was observed in lymphocytes from seven other malignant and nonmalignant sources. These results are the first to demonstrate a specific-binding protein for 1,25(OH)2D3 in lymphocytes from tissue and from these specific cell lines. The presence of this protein in some lymphocytes but not others may reflect the state of activation of the lymphocytes.
Binding, Competitive↗
The myotropic and plasma-calcium modulating effects of calcitonin gene-related peptide (CGRP).
Human and rat calcitonin gene-related peptides cause a dose-related contraction of guinea pig ileum, which is antagonised by an anti-histamine, mepyramine, and an anticholinergic compound, hyoscine. Both peptides also cause a positive inotropic and a positive chronotropic effect in the rat isolated auricle and these responses are antagonised by propranolol, a B adrenoceptor blocker. Further, the peptides lower plasma calcium levels in both rats and rabbits in a dose-related manner resembling calcitonin; in the rabbit, but not in the rat, the initial calcium lowering effect is succeeded by hypercalcaemia at higher doses, while in the chick, only the parathyroid hormone-like calcium-raising effect is seen.
Animals↗
Measurement of 1,25-dihydroxyvitamin D3 receptors in breast cancer and their relationship to biochemical and clinical indices.
Both normal and malignant breast tissue contain the specific receptor for 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). A recent study has shown its presence in 80% of surgically removed breast tumors, although only at low levels. We have measured the 1,25-(OH)2D3 receptor in breast tumors from 68 patients and have found it at similar frequency (75%) but at much higher concentrations (range, less than 1 to 30 fmol/mg protein). This receptor has the same characteristics as that measured in classic 1,25-(OH)2D3 target tissues and was distinguished by sucrose gradient centrifugation from plasma contaminants. Complete case histories and follow-up were available on 56 of these patients, and 1,25-(OH)2D3 receptor status (less than 8 or greater than or equal to 8 fmol/mg protein) was not related to the level of estrogen receptors, menopausal status, T-stage or histology of tumors, or presence of 99mTc phosphate hot spots on bone scans. The lack of relationship between the level of 1,25-(OH)2D3 receptors and other prognostic indicators suggests its potential as a new independent variable for assessing breast cancer patients. However, at this stage, 1,25-(OH)2D3 receptor status did not result in any significant difference in probability of survival or metastasis-free survival. Assessment of the importance of this variable for treatment or outcome must await an increased number of patients and a longer time since surgery.
Breast Neoplasms↗
[Are Stannius corpuscles the parathyroid glands of teleost fishes? Ultrastructural, cytologic and immunocytochemical arguments].
Parathyrin of Stannius corpuscles (PCS), glands which are restricted to Holostei and Teleostei, is closely related to mammalian parathyrin (PTH) secreted by the parathyroids [( 6] to [9]). In unstimulated and stimulated CS we have shown the same structure and cellular types that are described in mammalian parathyroids. We observed three types of cells; the two sorts of cells already described [14] present such a difference of density (Fig. 1) that type I may be compared to chief dark cells and type II to chief light cells. The difference between these two forms was particularly marked in activated CS; a similar observation has been reported concerning PT [15]. Furthermore, we have detected a third type of cell present either singly in unactivated CS or in small groups between chief cells in activated CS. They showed all the characteristics of oxyphil cells [17]; they present an extremely dense cytoplasm with numerous mitochondria and a typical stellate form with cytoplasmic processes extending between chief cells (Figs. 2, 3). In CS of untreated eels, we have shown by means of indirect immunocytology (using an immunserum raised against the active fragment 1-34 bPTH) that the immunostained reaction product was limited to dilated cisternae and ribosomes of the rough endoplasmic reticulum and to most of the granules in all the chief cells (Figs. 4, 5). No immunoreaction was observed in Golgi area. Oxyphil cells did not present an immune localization of PCS. CS are structurally and cytologically similar to mammalian PT; furthermore their chief cells synthesize, stock and secrete a substance immunologically similar to mammalian PTH; the exact function of oxyphil cells has to be demonstrated.
Animals↗