The Effect of Calcitonin Gene-Related Peptide (CGRP) on the Cytosolic Calcium Concentration and Force in Rat Intramural Coronary Arteries
The aim of this study was to investigate the mechanism of CGRP-induced relaxation in intramural rat coronary arteries. By using FURA-2 technique, cytosolic Ca2+-concentration ([Ca2+]i) was measured during contraction of the vascular smooth muscle with receptor-dependent agonist (tromboxane A2 analog...
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Wiley
2001-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1100/tsw.2001.443 |
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| author | M. Sheykhzade N.C.B. Nyborg |
| author_facet | M. Sheykhzade N.C.B. Nyborg |
| author_sort | M. Sheykhzade |
| collection | DOAJ |
| description | The aim of this study was to investigate the mechanism of CGRP-induced relaxation in intramural rat coronary arteries. By using FURA-2 technique, cytosolic Ca2+-concentration ([Ca2+]i) was measured during contraction of the vascular smooth muscle with receptor-dependent agonist (tromboxane A2 analogue U46619) and with high concentration of extracellular potassium. At a steady state of contraction, the increase in [Ca2+]i induced by 300 nM U46619 (100״x 14 nM, n = 7) was similar to that induced by 36 mM K+ (98 ״x 9 nM, n = 7). However, the active tension induced by 300 nM U46619 was significantly (p < 0.01) higher than that induced by 36 mM K+. CGRP concentration-dependently (10 pM - 10 nM) reduced both the [Ca2+]i and tension of coronary arteries precontracted with either U46619 or BAY K 8644, and also of resting coronary arteries in PSS. In 36 mM K+-depolarized arteries, CGRP reduced only the tension without affecting the [Ca2+]i. In 300 nM U46619 precontracted arteries, pretreatment with 10 μM thapsigargin significantly (p < 0.05) attenuated the CGRP-induced reduction in the tension (but not [Ca2+]i). In 300 nM U46619 precontracted arteries, pretreatment with either 100 nM charybdotoxin or 100 nM iberiotoxin or 10 nM felodipine significantly (p < 0.05) attenuated the CGRP-induced reduction in both [Ca2+]i and the tension. In contrast, 1 μM glibenclamide did not affect the CGRP-induced responses in these coronary arteries. In resting coronary arteries, only pretreatment with the combination of 1 μM glibenclamide and 100 nM charybdotoxin attenuated the CGRP-induced decrease in the [Ca2+]i and tension, suggesting a different mechanism of action for CGRP in resting coronary arteries. We conclude that CGRP relaxes precontracted rat coronary arteries via three mechanisms: (1) a decrease in [Ca2+]i by inhibiting the Ca2+ influx through membrane hyperpolarization mediated partly by activation of BKCa channels, (2) a decrease in [Ca2+]i presumably by sequestrating cytosolic Ca2+ into thapsigargin-sensitive Ca2+ storage sites, and (3) a decrease in the Ca2+ -sensitivity of the contractile apparatus. |
| format | Article |
| id | doaj-art-0d2fcbe3d30040e181b8d8f44c8fa0ef |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2001-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-0d2fcbe3d30040e181b8d8f44c8fa0ef2025-02-03T06:00:20ZengWileyThe Scientific World Journal1537-744X2001-01-011131310.1100/tsw.2001.443The Effect of Calcitonin Gene-Related Peptide (CGRP) on the Cytosolic Calcium Concentration and Force in Rat Intramural Coronary ArteriesM. Sheykhzade0N.C.B. Nyborg1Department of Pharmacology, The Royal Danish School of Pharmacy, Universitetsparken 2, 2100 Copenhagen Ø, DenmarkDepartment of Pharmacology, The Royal Danish School of Pharmacy, Universitetsparken 2, 2100 Copenhagen Ø, DenmarkThe aim of this study was to investigate the mechanism of CGRP-induced relaxation in intramural rat coronary arteries. By using FURA-2 technique, cytosolic Ca2+-concentration ([Ca2+]i) was measured during contraction of the vascular smooth muscle with receptor-dependent agonist (tromboxane A2 analogue U46619) and with high concentration of extracellular potassium. At a steady state of contraction, the increase in [Ca2+]i induced by 300 nM U46619 (100״x 14 nM, n = 7) was similar to that induced by 36 mM K+ (98 ״x 9 nM, n = 7). However, the active tension induced by 300 nM U46619 was significantly (p < 0.01) higher than that induced by 36 mM K+. CGRP concentration-dependently (10 pM - 10 nM) reduced both the [Ca2+]i and tension of coronary arteries precontracted with either U46619 or BAY K 8644, and also of resting coronary arteries in PSS. In 36 mM K+-depolarized arteries, CGRP reduced only the tension without affecting the [Ca2+]i. In 300 nM U46619 precontracted arteries, pretreatment with 10 μM thapsigargin significantly (p < 0.05) attenuated the CGRP-induced reduction in the tension (but not [Ca2+]i). In 300 nM U46619 precontracted arteries, pretreatment with either 100 nM charybdotoxin or 100 nM iberiotoxin or 10 nM felodipine significantly (p < 0.05) attenuated the CGRP-induced reduction in both [Ca2+]i and the tension. In contrast, 1 μM glibenclamide did not affect the CGRP-induced responses in these coronary arteries. In resting coronary arteries, only pretreatment with the combination of 1 μM glibenclamide and 100 nM charybdotoxin attenuated the CGRP-induced decrease in the [Ca2+]i and tension, suggesting a different mechanism of action for CGRP in resting coronary arteries. We conclude that CGRP relaxes precontracted rat coronary arteries via three mechanisms: (1) a decrease in [Ca2+]i by inhibiting the Ca2+ influx through membrane hyperpolarization mediated partly by activation of BKCa channels, (2) a decrease in [Ca2+]i presumably by sequestrating cytosolic Ca2+ into thapsigargin-sensitive Ca2+ storage sites, and (3) a decrease in the Ca2+ -sensitivity of the contractile apparatus.http://dx.doi.org/10.1100/tsw.2001.443 |
| spellingShingle | M. Sheykhzade N.C.B. Nyborg The Effect of Calcitonin Gene-Related Peptide (CGRP) on the Cytosolic Calcium Concentration and Force in Rat Intramural Coronary Arteries The Scientific World Journal |
| title | The Effect of Calcitonin Gene-Related Peptide (CGRP) on the Cytosolic Calcium Concentration and Force in Rat Intramural Coronary Arteries |
| title_full | The Effect of Calcitonin Gene-Related Peptide (CGRP) on the Cytosolic Calcium Concentration and Force in Rat Intramural Coronary Arteries |
| title_fullStr | The Effect of Calcitonin Gene-Related Peptide (CGRP) on the Cytosolic Calcium Concentration and Force in Rat Intramural Coronary Arteries |
| title_full_unstemmed | The Effect of Calcitonin Gene-Related Peptide (CGRP) on the Cytosolic Calcium Concentration and Force in Rat Intramural Coronary Arteries |
| title_short | The Effect of Calcitonin Gene-Related Peptide (CGRP) on the Cytosolic Calcium Concentration and Force in Rat Intramural Coronary Arteries |
| title_sort | effect of calcitonin gene related peptide cgrp on the cytosolic calcium concentration and force in rat intramural coronary arteries |
| url | http://dx.doi.org/10.1100/tsw.2001.443 |
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