Regulation of in vivo whole blood aggregation in rats by calcitonin gene related peptide

1998 ◽  
Vol 76 (7-8) ◽  
pp. 811-813 ◽  
Author(s):  
Brian P Booth ◽  
Ho-Leung Fung
Keyword(s):  
Blood Pressure ◽  
Whole Blood ◽  
Ex Vivo ◽  
Calcitonin Gene Related Peptide ◽  
Physiological Control ◽  
Duration Of Action ◽  
Related Peptide ◽  
Arterial Blood ◽  
Calcitonin Gene

The purpose of these experiments was to determine whether calcitonin gene related peptide (CGRP) mediates physiological control of platelet function in vivo. Rat blood pressure was continuously monitored via a femoral arterial cannula, and whole blood aggregation was assessed periodically ex vivo with an impedance aggregometer before and following a 1.4 nmol/kg bolus dose of CGRP8-37, a specific receptor antagonist of CGRP. Mean arterial blood pressure was not significantly affected by CGRP8-37 over a 30-min period (p > 0.05). However, whole blood aggregation increased by 38.4 ± 18.0% (p < 0.01) and 32.0 ± 11.2% (p < 0.05), at 5 and 15 min post CGRP8-37, respectively, when compared with control. Whole blood aggregation was not significantly different from control at 30 min (p > 0.05), suggesting a relatively short duration of action for in vivo CGRP8-37. These data suggest that CGRP contributes to the maintenance of hemostasis, and that this function may be more important than the better known vasodilatatory effects of this neuropeptide.Key words: hemostasis, calcitonin gene related peptide (CGRP), CGRP8-37, blood pressure, platelet aggregation.

CGRP-dependent signalling pathways involved in mouse models of GTN- cilostazol- and levcromakalim-induced migraine

Cephalalgia ◽  
2021 ◽  
pp. 033310242110388
Author(s):  
Sarah L Christensen ◽  
Rikke H Rasmussen ◽  
Charlotte Ernstsen ◽  
Sanne La Cour ◽  
Arthur David ◽  
...  
Keyword(s):  
Glyceryl Trinitrate ◽  
Mouse Models ◽  
Transient Receptor Potential ◽  
Ex Vivo ◽  
Calcitonin Gene Related Peptide ◽  
Signalling Pathways ◽  
Receptor Antagonism ◽  
Related Peptide ◽  
Calcitonin Gene

Background Knowledge of exact signalling events during migraine attacks is lacking. Various substances are known to trigger migraine attacks in patients and calcitonin gene-related peptide antagonising drugs are effective against migraine pain. Here, we investigated the signalling pathways involved in three different mouse models of provoked migraine and relate them to calcitonin gene-related peptide and other migraine-relevant targets. Methods In vivo mouse models of glyceryl trinitrate-, cilostazol- and levcromakalim-induced migraine were applied utilising tactile sensitivity to von Frey filaments as measuring readout. Signalling pathways involved in the three models were dissected by use of specific knockout mice and chemical inhibitors. In vivo results were supported by ex vivo wire myograph experiments measuring arterial dilatory responses and ex vivo calcitonin gene-related peptide release from trigeminal ganglion and trigeminal nucleus caudalis from mice. Results Glyceryl trinitrate-induced hypersensitivity was dependent on both prostaglandins and transient receptor potential cation channel, subfamily A, member 1, whereas cilostazol- and levcromakalim-induced hypersensitivity were independent of both. All three migraine triggers activated calcitonin gene-related peptide signalling, as both receptor antagonism and antibody neutralisation of calcitonin gene-related peptide were effective inhibitors of hypersensitivity in all three models. Stimulation of trigeminal ganglia and brain stem tissue samples with cilostazol and levcromakalim did not result in release of calcitonin gene-related peptide, and vasodilation following levcromakalim stimulation was independent of CGRP receptor antagonism. Conclusion The mouse models of glyceryl trinitrate-, cilostazol- and levcromakalim- induced migraine all involve calcitonin gene-related peptide signalling in a complex interplay between different cell/tissue types. These models are useful in the study of migraine mechanisms.

scholarly journals The Role of Calcitonin Gene-Related Peptide in the in Vivo Pituitary-Adrenocortical Response to Acute Hypoxemia in the Late-Gestation Sheep Fetus

Endocrinology ◽  
2005 ◽  
Vol 146 (11) ◽  
pp. 4871-4877 ◽  
Author(s):  
A. S. Thakor ◽  
D. A. Giussani
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Late Gestation ◽  
Blood Gas ◽  
Plasma Acth ◽  
Related Peptide ◽  
Arterial Blood ◽  
Calcitonin Gene ◽  
Sheep Fetus ◽  
Cgrp Antagonist

This study tested the hypothesis that calcitonin gene-related peptide (CGRP) has a role in mediating the in vivo fetal adrenal glucocorticoid response to acute stress. The hypothesis was tested by investigating the effects of fetal treatment with a selective CGRP antagonist on plasma ACTH and cortisol responses to acute hypoxemia in the late-gestation sheep fetus. Under anesthesia, six fetuses at 0.8 of gestation were surgically instrumented with vascular catheters. Five days later, fetuses were subjected to 0.5-h hypoxemia during treatment with either iv saline or a CGRP antagonist, in randomized order, on different days. Treatment started 30 min before hypoxemia and ran continuously until the end of the challenge. Arterial blood samples were collected for plasma ACTH and cortisol measurements (RIA) and blood gas monitoring. CGRP antagonism did not alter basal arterial blood gas or endocrine status. During hypoxemia, similar falls in arterial partial pressure of oxygen occurred in all fetuses. During saline infusion, acute hypoxemia induced significant increases in fetal ACTH and cortisol concentrations. During CGRP antagonism, the pituitary-adrenal responses were markedly attenuated. Correlation of paired plasma ACTH and cortisol values from all individual fetuses during normoxia and hypoxemia showed positive linear relationships; however, neither the slope nor the intercept of the peptide-steroid relationship was affected by CGRP antagonism. These data support the hypothesis that CGRP is involved in the in vivo regulation of fetal adrenocortical steroidogenesis during acute hypoxemia. In addition, the data reveal that CGRP may have a role in the control of other components of the hypothalamo-pituitary-adrenal axis during stimulated conditions in fetal life.

Induction of insulin resistance in vivo by amylin and calcitonin gene-related peptide

Diabetes ◽  
1990 ◽  
Vol 39 (2) ◽  
pp. 260-265 ◽  
Author(s):  
J. M. Molina ◽  
G. J. Cooper ◽  
B. Leighton ◽  
J. M. Olefsky
Keyword(s):  
Insulin Resistance ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene

scholarly journals Induction of Insulin Resistance In Vivo by Amylin and Calcitonin Gene-Related Peptide

Diabetes ◽  
1990 ◽  
Vol 39 (2) ◽  
pp. 260-265 ◽  
Author(s):  
J. M. Molina ◽  
G. J. S. Cooper ◽  
B. Leighton ◽  
J. M. Olefsky
Keyword(s):  
Insulin Resistance ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene

scholarly journals Acetaminophen (Paracetamol) Metabolites Induce Vasodilation and Hypotension by Activating Kv7 Potassium Channels Directly and Indirectly

2020 ◽  
Vol 40 (5) ◽  
pp. 1207-1219 ◽  
Author(s):  
Jennifer van der Horst ◽  
Rian W. Manville ◽  
Katie Hayes ◽  
Morten B. Thomsen ◽  
Geoffrey W. Abbott ◽  
...  
Keyword(s):  
Preventive Intervention ◽  
Ex Vivo ◽  
Calcitonin Gene Related Peptide ◽  
Mesenteric Arteries ◽  
Benzoquinone Imine ◽  
Kv7 Channels ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Perivascular Nerves ◽  
Life Threatening

Objective: Intravenous acetaminophen/paracetamol (APAP) is well documented to cause hypotension. Since the patients receiving intravenous APAP are usually critically ill, any severe hemodynamic changes, as with those associated with APAP, can be life-threatening. The mechanism underlying this dangerous iatrogenic effect of APAP was unknown. Approach and Results: Here, we show that intravenous APAP caused transient hypotension in rats, which was attenuated by the Kv7 channel blocker, linopirdine. APAP metabolite N-acetyl-p-benzoquinone imine caused vasodilatation of rat mesenteric arteries ex vivo. This vasodilatation was sensitive to linopirdine and also the calcitonin gene-related peptide antagonist, BIBN 4096. Further investigation revealed N-acetyl-p-benzoquinone imine stimulates calcitonin gene-related peptide release from perivascular nerves, causing a cAMP-dependent activation of Kv7 channels. We also show that N-acetyl-p-benzoquinone imine enhances Kv7.4 and Kv7.5 channels overexpressed in oocytes, suggesting that it can activate Kv7.4 and Kv7.5 channels directly, to elicit vasodilatation. Conclusions: Direct and indirect activation of Kv7 channels by the APAP metabolite N-acetyl-p-benzoquinone imine decreases arterial tone, which can lead to a drop in blood pressure. Our findings provide a molecular mechanism and potential preventive intervention for the clinical phenomenon of intravenous APAP-dependent transient hypotension.

scholarly journals Calcitonin gene-related peptide promotes Schwann cell proliferation.

1995 ◽  
Vol 129 (3) ◽  
pp. 789-796 ◽  
Author(s):  
L Cheng ◽  
M Khan ◽  
A W Mudge
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Neutral Endopeptidase ◽  
Calcitonin Gene Related Peptide ◽  
Intracellular Camp ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Glial Growth Factor

Schwann cells in culture divide in response to defined mitogens such as PDGF and glial growth factor (GGF), but proliferation is greatly enhanced if agents such as forskolin, which increases Schwann cell intracellular cAMP, are added at the same time as PDGF or GGF (Davis, J. B., and P. Stroobant. 1990. J. Cell Biol. 110:1353-1360). The effect of forskolin is probably due to an increase in numbers of PDGF receptors (Weinmaster, G., and G. Lemke. 1990. EMBO (Eur. Mol. Biol. Organ.) J. 9:915-920. Neuropeptides and beta-adrenergic agonists have been reported to have no effect on potentiating the mitogenic response of either PDGF or GGF. We show that the neuropeptide calcitonin gene-related peptide (CGRP) increases Schwann cell cAMP levels, but the cells rapidly desensitize. We therefore stimulated the cells in pulsatile fashion to partly overcome the effects of desensitization and show that CGRP can synergize with PDGF to stimulate Schwann cell proliferation, and that CGRP is as effective as forskolin in the pulsatile regime. CGRP is a good substrate for the neutral endopeptidase 24.11. Schwann cells in vivo have this protease on their surface, so the action of CGRP could be terminated by this enzyme and desensitization prevented. We therefore suggest that CGRP may play an important role in stimulating Schwann cell proliferation by regulating the response of mitogenic factors such as PDGF.

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