The hormonal regulation of extracellular calcium.
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Animals↗
Biomedical subjects
I MacIntyre
Publications and source records attributed to I MacIntyre.
Potent vasodilator activity of calcitonin gene-related peptide in human skin.
We have recently shown that the novel neuropeptide calcitonin gene-related peptide, CGRP, is a potent vasodilator. In this paper we report a detailed study of the effects of CGRP in human skin. CGRP induces a clearly defined, long-lasting erythema. We have measured the effect of CGRP on blood flow in human skin using a laser Doppler technique and have demonstrated increased local blood flow that persists for a number of hours. We compared the response of CGRP with other known vasodilators [histamine, prostaglandin (PG) E2, PGI2, substance P, and vasoactive intestinal peptide (VIP)] in the skin, and in all subjects the erythema induced by CGRP was more persistent than that induced by the other mediators tested. Except at high doses the local vasodilatation induced by CGRP was not associated with a wheal and flare as seen with histamine, substance P, and VIP. CGRP is an extremely potent vasodilator and if released into the circulation, or locally from peripheral nerve endings, it could have a role in the regulation of blood flow in both physiologic and pathologic conditions; CGRP may be the endogenous mediator of the flare in the triple response. A deficiency in CGRP secretion or action could be an important component of peripheral vascular disease. Some flushing reactions (e.g., those associated with medullary thyroid carcinoma) may result from circulating CGRP.
Adult↗
Calcitonin gene-related peptide: a potent dilator of human epicardial coronary arteries.
To investigate the action of calcitonin gene-related peptide (CGRP) on human epicardial coronary arteries, six patients received intracoronary CGRP at doses of 50,100, and 200 ng/min. The effect of CGRP was measured angiographically with a computerized analysis system. A dose-dependent increase in coronary arterial diameter was observed. At the highest dose there were 34%, 7%, 38%, and 40% mean increases in the diameters of the circumflex, proximal, mid, and distal left anterior descending arteries, respectively. No further increase in diameter was found after a subsequent dose of 1 mg intracoronary isosorbide dinitrate. Prior infusion of CGRP did not prevent coronary arterial spasm induced by ergonovine in two patients with variant angina, but a subsequent bolus of CGRP partially relieved the spasm. We propose that CGRP has a role in the regulation of coronary vascular smooth muscle tone.
Angina Pectoris↗
Human synthetic calcitonin gene-related peptide inhibits bone resorption in vitro.
The calcitonin gene-related peptide (CGRP) is a peptide which normally circulates. It is encoded by the calcitonin gene, whose precise function is unknown. Since it has recently been shown that human CGRP (hCGRP) lowers plasma calcium levels in both the rat and the rabbit, we examined the in vitro effects of human synthetic CGRP on bone resorption (as measured by 45Ca release) stimulated by PTH, prostaglandin E2, and 1,25-dihydroxyvitamin D3. CGRP caused a dose-dependent inhibition of PTH-stimulated resorption, with 50% inhibition at approximately 5 X 10(-8) M CGRP. The inhibitory effects of CGRP on PTH-mediated bone resorption were not due to toxic effects, since bones preincubated with CGRP for 48 h were subsequently able to respond to PTH. The inhibitory activity of CGRP in the rat was approximately 3 orders of magnitude less potent than that of human calcitonin. In contrast to the effects of calcitonin, a marked inhibition of PTH-stimulated bone resorption was still observed after 96 h in the continued presence of CGRP. CGRP (10(-6)-10(-8) M) also inhibited resorption stimulated by prostaglandin and 1,25-dihydroxyvitamin D3 in a dose-dependent manner, but had no significant effect on basal bone resorption. In conclusion, these data show that hCGRP inhibits hormone-stimulated bone resorption in vitro. Although it is less potent than calcitonin in the rat, CGRP has been shown to have potency comparable to that of calcitonin in other species, and therefore, a role for CGRP as a therapeutic agent in states of increased bone resorption cannot be ruled out.
Animals↗
The origin of circulating calcitonin gene-related peptide in the rat.
It is known that in addition to the calcitonin precursor the calcitonin gene also encodes a novel peptide, calcitonin gene-related peptide (CGRP). This potent vasodilator has been found in the circulation of man. This present study demonstrates that CGRP is also found in the circulation of the rat and that plasma CGRP comes from two different sources: the thyroid, a major source in old rats, and the perivascular nerves probably at all ages.
Adrenal Glands↗
Localization of calcitonin gene-related peptide in the organ of Corti of the rat: an immunohistochemical study.
The localization of calcitonin gene-related peptide (CGRP)-like immunoreactive (CGRPI) structures in the cochlea was examined in the rat using immunocytochemistry. Numerous CGRPI fibers entered the organ of Corti in the intraganglionic spiral bundle and formed a dense fiber patch at the base of the inner hair cells. Much fewer, but still a significant number of CGRPI fibers were seen at the synaptic region of the outer hair cells. Since no immunoreactive cells were seen in the organ of Corti and spinal ganglion, these fibers may be one of the major components of the olivocochlear bundles originated from the superior olivary complex.
Animals↗
Calcium supplements and postmenopausal osteoporosis.
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Animals↗
Circulating CGRP comes from the perivascular nerves.
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Animals↗
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↗