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Biomedical subjects

I MacIntyre

Publications and source records attributed to I MacIntyre.

At least 73 records · Page 4Linked to original sources
PubMed1988

Vasodilatation by calcitonin gene-related peptide and by substance P: a comparison of their effects on resistance and capacitance vessels of human forearms.

A comparison has been made of the effects of the potent vasodilating peptide calcitonin gene-related peptide (CGRP) and substance P (SP) on resistance and capacitance vessels of normal subjects. Brachial artery infusion of 1.25 to 10 pmol/min CGRP and of 0.25 to 1.5 pmol/min SP produced maximal increases in forearm blood flow (177 +/- 75% and 198 +/- 50%, respectively), as measured by venous occlusion plethysmography. The vasodilation due to CGRP was prolonged, with a half-life of biological effect of approximately 18 min, while that due to SP was of short duration, with a half-life of biological effect of approximately 15 sec. There was rapid development of tachyphylaxis to the effects of arterial infusion of SP, but not of CGRP, during a prolonged infusion at one dose. CGRP did not alter the diameter of a superficial hand vein, either at rest or when the vein was constricted by a simultaneous infusion of norepinephrine or by the single deep breath reflex. In contrast, SP caused dilatation of veins preconstricted with norepinephrine, although the effect was only transient and dose-response curves could not be constructed. The venoconstrictor response to a single deep breath was abolished by SP. Simultaneous arterial infusion of both peptides produced at least additive, and possibly synergistic, effects on forearm blood flow. We propose that both CGRP and SP have a role in the regulation of vascular smooth muscle tone.

Adult↗
PubMed1988

A sensitive and specific two-site enzyme-immunoassay for human calcitonin using monoclonal antibodies.

A highly sensitive, specific and rapid two-site enzyme-immunometric assay (EIA) for the measurement of immunoreactive (ir) human calcitonin (hCT) in human plasma was developed using high-affinity monoclonal antibodies. The assay was validated in terms of sensitivity, specificity and reproducibility and its performance compared with that of a radioimmunoassay (RIA) employing a polyclonal antiserum. The sensitivity of the overnight EIA (2 pmol/l) was comparable with the long-incubation (7 days) RIA. The overnight RIA had a sensitivity of 10 pmol/l. The inter- and intra-assay variations of the EIA were less than 12%. Some related and non-related peptides were compared with synthetic hCT for cross-reactivity in the assay and were found to be negative. The mean recovery of added synthetic hCT from plasma of normal volunteers was 96%. Both RIA and EIA have been applied to the measurement of ir-hCT in normal volunteers and in patients with medullary carcinoma of the thyroid. In both groups, the level of ir-hCT measured by EIA was found to be lower than that measured by RIA, presumably due to the ability of the more specific EIA to detect only the 'mature' form of the hormone. EIA offers an attractive alternative to the more cumbersome and lengthy RIA in current usage, with the added advantage of employing a non-isotopic label.

Alkaline Phosphatase↗
PubMed1988

Development and performance of a highly sensitive carboxyl-terminal-specific radioimmunoassay of calcitonin gene-related peptide.

The calcitonin genes encode a small family of peptides: the circulating hormone calcitonin; its flanking peptide, katacalcin; and a third novel peptide, calcitonin gene-related peptide (CGRP). CGRP is a potent vasodilator and a major circulating product from the calcitonin genes; it may be a physiologically important regulator of blood flow in humans. High concentrations of circulating CGRP are found in medullary thyroid carcinoma. We report the development and validation of a highly sensitive (detection limit 500 amol per tube) radioimmunoassay of CGRP involving a high-affinity antibody directed against the carboxyl terminus of the molecule and a highly pure tracer. The assay is precise, robust, and reproducible, and is therefore a potentially useful analytical method for studying the normal and abnormal physiology of this peptide.

Antibody Specificity↗
PubMed1987

Transient appearance of calcitonin gene-related peptide-like immunoreactive fibers in the developing cerebellum of the rat.

A plexus of calcitonin gene-related peptide (CGRP)-containing fibers were transiently found in the developing cerebellum of the rat by means of the indirect immunofluorescent method. CGRP-like immunoreactive fibers appeared in the cerebellum by embryonic day 22. Immunoreactive fibers rapidly increased and these made a dense plexus in the Purkinje cell layer by postnatal day 2. However, only a few if any immunoreactive fibers were seen in the Purkinje cell layer or molecular layer of adult rats.

Animals↗
PubMed1987

Calcitonin gene-related peptide-like immunoreactive sensory fibers form synaptic contact with sympathetic neurons in the rat celiac ganglion.

The present study demonstrates synaptic contact between calcitonin gene-related peptide (CGRP)-like immunoreactive axon terminals and sympathetic neurons in the rat celiac ganglion. Our observations suggest that sensory ganglion neurons directly regulate the sympathetic activity via synapses, because CGRP immunoreactive (CGRPI) fibers in this ganglion are supplied by the sensory ganglia.

Animals↗
PubMed1987

Distribution and origin of calcitonin gene-related peptide in the rat stomach and duodenum: an immunocytochemical analysis.

We studied the three-dimensional distribution of structures with calcitonin gene-related peptide-like immunoreactivity (CGRPI) in the rat stomach and duodenum, including the origins of these structures, using indirect immunofluorescence in both muscle strips and frozen sections. There was a very dense meshwork of CGRPI fibers in the circular and longitudinal muscle layers, and also in the myenteric and submucous plexuses of the stomach and duodenum. No CGRPI neurons were seen in the stomach, even in rats treated with colchicine; in the duodenum, there was a group of CGRPI cells in the myenteric and submucous ganglia. No regional differences were seen in the stomach and duodenum. We found by experimental manipulations that CGRPI fibers in the stomach were exclusively extrinsic in origin; some of such fibers in the duodenum were intrinsic in origin, though most were supplied by CGRPI cells outside the duodenum.

Animals↗
PubMed1987

Calcitonin gene-related peptide inhibits osteoclastic bone resorption: a comparative study.

Besides the calcitonin (CT) precursor, the calcitonin gene also encodes another peptide--calcitonin gene-related peptide (CGRP). We have previously reported that CGRP lowers plasma calcium in the rat. In the present study we have evaluated the effect of CGRP on resorption of bone by isolated rat osteoclasts and have compared these effects to those produced by calcitonins from three species (salmon, pig, and human calcitonins). There was a significant inhibition of bone resorption with rat calcitonin gene-related peptide (rCGRP) at a 1000-fold higher dose than that used for human CT. This effect well explains the CT-like effect of CGRP seen in the in vivo rat CT bioassay. Our results suggest that though CGRP may not be involved in the hormonal control of plasma calcium, the peptide may be an important local regulator of bone cell function.

Animals↗
PubMed1987

The presence of calcitonin gene-related peptide in human cerebrospinal fluid.

This study demonstrates the presence of calcitonin gene-related peptide (CGRP) in human cerebrospinal fluid (CSF) using specific and sensitive radioimmunoassay, together with gel-permeation and high performance liquid chromatography (HPLC). The median immunoreactive CGRP (i-CGRP) level from 158 CSF specimens was 8.0 pmol/l, as measured with an antiserum recognizing the whole molecule of CGRP (CC-2/1) and 12.0 pmol/l with an antiserum recognizing the C-terminal region of CGRP (CG-39). CSF samples with high protein concentration (greater than or equal to 0.6 g/l) had a median level of i-CGRP of 18.4 pmol/l when measured with antiserum CC-2/1 and 23.0 pmol/l with CG-39, while samples with 'normal' protein concentrations (less than 0.6 g/l) had much lower values, with median levels of 7.0 and 11.0 pmol/l, with the two antisera, respectively. Gel-permeation chromatography and HPLC studies revealed multiple peaks of i-CGRP, consistent with forms with different molecular weights. However, on HPLC, the major peak of i-CGRP corresponded to the elution position of the synthetic hCGRP(1-37) and was able to bind to a CGRP specific receptor preparation suggesting that it may be biologically active.

Calcitonin Gene-Related Peptide↗
PubMed1987

Human calcitonin gene-related peptide activates adenylate cyclase and releases prostacyclin from human umbilical vein endothelial cells.

1 Endothelial cells of human umbilical vein were isolated and cultured in vitro. 2 In these cells there was a concentration-dependent release of prostacyclin and activation of adenylate cyclase by human calcitonin gene-related peptide (hCGRP). The concentration of hCGRP for half-maximum activation of adenylate cyclase (Kact) by hCGRP was 190 nM. 3 Bradykinin induced a ten fold greater release of prostacyclin than CGRP, but did not activate adenylate cyclase. 4 hCGRP may exert its potent vasodilator properties by stimulating release of vasorelaxant substances, including prostacyclin from endothelial cells.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Biology of peptides from the calcitonin genes.

Despite being products from the same gene, there is clearly a marked divergence in the distribution and physiological role of calcitonin and CGRP. Whereas calcitonin is predominantly distributed in the thyroid, CGRP is abundant in the nervous system throughout the body. Though the peptides have only weak structural homologies, a generally similar conformation enables them to interact at each other's receptors. Hence the pharmacological effects of the peptides faintly resemble one another. Calcitonin receptors are mainly found on osteoclasts and at certain sites in the nervous system. CGRP binding sites are abundant in the cerebellum and blood vessels. Calcitonin is a circulating hormone controlling osteoclastic activity. CGRP acts as a neurotransmitter or neuromodulator centrally, and released from perivascular nerve terminals, it modulates arteriolar tone. Released from motoneurones, CGRP may also play a trophic role regulating the muscle acetylcholine receptor state. The next decade should establish the physiological role of CGRP and the regulation of the expression of the calcitonin/CGRP gene complex.

Animals↗
PubMed1987

Regional distribution of calcitonin gene-related peptide and its specific binding sites in rats with particular reference to the nervous system.

The concentration of calcitonin gene-related peptide (CGRP) in rat tissue extracts was determined by a specific and sensitive radio-immunoassay, and the distribution of its specific binding sites was assessed by radioligand binding studies. A high concentration of immunoreactive CGRP was found at all levels of the spinal cord, in the trigeminal nucleus, in trigeminal and dorsal root ganglia, in the thyroid gland, in blood vessels and in nerves. The highest density of specific binding sites was detected in the cerebellum, where the CGRP content was minimal. The dorsal portion of the spinal cord contained a high concentration of CGRP and its specific binding sites. Specific binding of 125I-CGRP was also demonstrated in a number of other areas of the brain and in certain peripheral tissues. Among the other tissues examined, the spleen, adrenal gland, penis, lungs, bladder, heart and blood vessels all contained a large number of CGRP binding sites, whereas only a negligible number of sites were found in ganglia, nerves, muscle, kidney and liver. The distribution of CGRP and its specific binding sites demonstrated here suggests that CGRP is a neuropeptide with multiple physiological roles.

Animals↗
PubMed1987

Regional and total skeletal measurements in the early postmenopause.

In a cross-sectional study of 70 early postmenopausal women, regional bone measurements were compared with total body calcium (TBCa). Spinal and forearm trabecular bone were mainly related to age and time since menopause. In contrast, TBCa and forearm integral (cortical and trabecular) and cortical bone were unrelated to age, although the time since menopause also had some influence. Forearm integral and cortical bone measurements were quite well correlated with TBCa (r = 0.84 and 0.73, respectively, P less than 0.001). The correlation between spinal bone measurements and any of the forearm measurements, even purely trabecular bone, was weak (r less than 0.52, P less than 0.001). Our results show quite clearly that forearm bone measurements cannot be used to predict bone density in the vertebrae. Loss of ovarian function affects bone in general, and trabecular bone in particular. Bone measurements at specific anatomical sites are clearly necessary for studies of metabolic bone diseases and their response to treatment.

Adult↗
PubMed1987

A direct action of human calcitonin gene-related peptide on isolated osteoclasts.

The calcitonin gene encodes a small family of peptides: calcitonin, calcitonin gene-related peptide (CGRP) and katacalcin. Whereas calcitonin is concerned with skeletal maintenance, the function, if any, of katacalcin is still unknown. In the present study we have assessed resorption of human cortical bone substrate by isolated rat osteoclasts and have shown that CGRP acts directly on the osteoclast to inhibit bone resorption. The three CGRP peptides (rat, human(alpha) and human(beta) caused an almost equivalent decrease in osteoclastic bone resorption and were approximately 1000-fold less potent than human calcitonin in this respect. The responses of human calcitonin and human CGRP(alpha) were additive. Furthermore, prior treatment with trypsin to destroy receptors abolished the responsiveness of osteoclasts to CGRP and calcitonin. The carboxyl- and amino-terminal fragments of CGRP were found not to inhibit bone resorption, suggesting that the whole molecule of CGRP is necessary for biological activity. We have therefore suggested that the calcitonin-like effects of CGRP, seen both in vivo in the rat bioassay and in vitro in organ cultures, are due to the direct action of CGRP on the osteoclast, probably mediated through the calcitonin receptor. Though it is unlikely that CGRP is involved in the regulation of plasma calcium, the peptide may be an important local regulator of bone cell function.

Animals↗
PubMed1987

Calcitonin and the peptides from the calcitonin gene.

The alpha-calcitonin gene encodes a small family of peptides: calcitonin, katacalcin, and calcitonin gene-related peptide (CGRP). Calcitonin and katacalcin are produced from one precursor and CGRP from another. Calcitonin and katacalcin come mainly from the thyroid, while CGRP is present in both the thyroid and the central nervous system. Calcitonin is concerned with skeletal integrity, while the function of katacalcin, if any, is unknown. The secretion of calcitonin is, in part, estrogen dependent, and it appears likely that a postmenopausal decline in calcitonin secretion is a factor in the development of postmenopausal osteoporosis. It is possible that calcitonin may prove useful in the prevention and perhaps the treatment of this condition. CGRP, conversely, is one of the most potent vasodilators known and probably plays an important physiologic role in the control of vessel tone and blood flow. CGRP may also have a role as neurotransmitter or neuromodulator.

Amino Acid Sequence↗
PubMed1986

Distribution and origins of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)- and neuropeptide Y (NPY)-containing nerve fibers in the pineal gland of gerbils.

In the pineal gland of gerbils, substance P (SP)-, calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)- and neuropeptide Y (NPY)-containing nerve fibers were demonstrated immunohistochemically. After intrapineal injection of biotin-wheat germ agglutinin, origins of fibers were examined by the combined technique of tracing method and immunohistochemistry. It was confirmed that SP- and CGRP-fibers originated from the trigeminal ganglion, VIP-fibers from the pterygopalatine ganglion and NPY-fibers from the superior cervical ganglion.

Animals↗