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Biomedical subjects

I MacIntyre

Publications and source records attributed to I MacIntyre.

At least 55 records · Page 3Linked to original sources

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

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

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

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

A physiological role for calcitonin: protection of the maternal skeleton.

Plasma-calcitonin levels, measured with an established and reliable extraction radioimmunoassay technique, were significantly higher throughout normal pregnancy and lactation than in normal non-pregnant women, and were not immediately influenced by the acute stimulation of breast-feeding. Thus, more calcitonin circulates at times of physiologically increased calcium need. It is suggested that an important function of calcitonin is the protection of the healthy maternal skeleton from excessive resorption by opposing the resorptive action of 1,25-dihydroxycholecalciferol on bone.

Adolescent

The role of the kidney in vitamin D metabolism.

The kidney should be regarded as an organ of central importance in the regulation of calcium metabolism. Its secretion product, 1 alpha,25(OH)2D3, is regulated by several factors, including the calcium and phosphorus content of the diet, parathyroid hormone and the level of 1 alpha,25(OH)2D3 itself. The main occasions in health where 1 alpha,25(OH)2D3 secretion is enhanced are during growth and reproduction. In these situations the secretion of this new renal hormone is under at least partial control of growth hormone and prolactin.

Animals

Effect of oestrogen and 1,25-dihydroxycholecalciferol on 25-hydroxycholecalciferol metabolism in primary chick kidney-cell cultures.

Primary cultures of chick kidney cells convert 25-hydroxycholecalciferol into more-polar metabolites. Cells from vitamin D-deficient chicks have high 25-hydroxycholecalciferol 1 alpha-hydroxylase (1 alpha-hydroxylase) activity, but no 25-hydroxycholecalciferol 24-hydroxylase (24-hydroxylase) activity. Physiological concentrations of 1,25-dihydroxycholeclaciferol suppress 1 alpha-hydroxylase and induce 24-hydroxylase activity. The inhibition of 1 alpha-hydroxylase preceded the induction of 24-hydroxylase. In contrast, oestradiol-17 beta had no effect on the activity of either hydroxylase under a variety of experimental conditions. These results clearly demonstrate that 1,25-dihydroxycholecalciferol, but not oestrogen, acts directly on the kidney cells to regulate the metabolism of 25-hydroxycholecalciferol.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase

Relative deficiency of plasma-calcitonin in normal women.

A new radioimmunoassay technique was used to measure plasma-calcitonin in normal subjects. Plasma-calcitonin concentrations in women were less than 25% of those in men, and were often undetectable. However, during pregnancy or administration of the oestrogen-progestagen contraceptive pill, plasma-calcitonin equalled or exceeded male concentrations. These findings are consistent with an effect on calcitonin production of normal male testosterone concentrations and concentrations of the sex steroids during pregnancy. Calcitonin may protect the skeleton during calcium stress. Further, although it is unknown whether a deficiency of the hormone plays a role in postmenopausal osteoporosis, this is now a definite possibility which requires urgent investigation.

Adolescent

A survey of the hormonal factors that control calcium metabolism.

(1) Vitamin D is the precursor of an extremely potent calcium regulating hormone, 1,25(OH)2D3, which is secreted by the kidney. (2) The secretion of 1,25(OH)2D3 by the kidney is influenced by the calcium and phosphorus content of the diet, parathyroid hormone, and 1,25(OH)2D3 itself. (3)Prolactin and growth hormone are importnat regulators of vitamin D metabolism during pregnancy and growth.

Animals