Abstract
The presence and vasoactive effects of native calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A (NKA) were studied on isolated small branches of the coeliac artery from Atlantic cod, Gadus morhua, using immunohistochemistry and myograph recordings, respectively. Immunohistochemistry revealed nerve fibers containing CGRP- and SP/NKA-like material running along the wall of the arteries. CGRP induced vasorelaxation of precontracted arteries with a pD2 value of 8.54 ± 0.17. Relaxation to CGRP (10−8 M) was unaffected by l-NAME (3 × 10−4 M) and indomethacin (10−6 M) suggesting no involvement of nitric oxide or prostaglandins in the CGRP-induced relaxation. SP and NKA (from 10−10 to 3 × 10−7 M) contracted the unstimulated arteries at concentrations from 10−8 M and above in 42% and 33%, respectively, of the vessels. It is concluded that the innervation of the cod celiac artery includes nerves expressing CGRP-like and tachykinin-like material, and that a vasodilatory response to CGRP is highly conserved amongst vertebrates while the response to tachykinins is more variable.
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Abbreviations
- CGRP:
-
Calcitonin gene-related peptide
- CY3:
-
Cyanine 3
- DMSO:
-
Dimethyl sulfoxide
- DTAF:
-
Dichlorotriazinylaminofluorescein
- l-NAME:
-
NG-nitro-l-arginine methyl ester
- NK1:
-
Neurokinin 1
- NK2:
-
Neurokinin 2
- NK3:
-
Neurokinin 3
- NKA:
-
Neurokinin A
- NKB:
-
Neurokinin B
- NO:
-
Nitric oxide
- PBS:
-
Phosphate buffered saline
- SP:
-
Substance P
References
Abdelrahman A, Wang YX, Chang SD, Pang CCY (1992) Mechanism of the vasodilator action of CGRP in conscious rats. Br J Pharmacol 106:45–48
Amerini S, Mantelli L, Ledda F (1993) Nitric oxide is not involved in the effects induced by non-adrenergic non-cholinergic stimulation and calcitonin gene-related peptide in the rat mesenteric vascular bed. Neuropeptides 25:51–56. doi:10.1016/0143-4179(93)90068-L
Axelsson M, Fritsche R (1991) Effect of exercise, hypoxia and feeding on the gastrointestinal blood flow in the Atlantic cod, Gadus morhua. J Exp Biol 158:181–198
Axelsson M, Fritsche R, Holmgren S, Grove DJ (1991) Gut blood flow in the estuarine crocodile, Crocodylus porosus. Acta Physiol Scand 142:509–516
Bell D, McDermott BJ (1996) Calcitonin gene-related peptide in the cardiovascular system: characterization of receptor populations and their (patho) physiological significance. Pharmacol Rev 48:253–288
Brain DS, Grant AD (2004) Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev 84:903–934. doi:10.1152/physrev.00037.2003
Courtice GP, Burcher E, Carlo-Stellar R, Conlon JM (1993) Cardiovascular effects of amphibian and mammalian tachykinins in the toad, Bufo marinus. Neuropeptides 24:171–176. doi:10.1016/0143-4179(93)90082-L
D’Orleans-Juste P, Dion S, Drapeau G, Regoli D (1986) Different receptors are involved in the endothelium-mediated relaxation and the smooth muscle contraction of the rabbit pulmonary artery in response to SP and related neurokinins. Eur J Pharmacol 125:37–44. doi:10.1016/0014-2999(86)90081-6
Gibbins IL, Furness JB, Costa M, Macintyre I, Hillyard CJ, Girgis S (1985) Co-localization of calcitonin gene-related peptide-like immunoreactivity with substance P in cutaneous, vascular and visceral sensory neurons of guinea pigs. Neurosci Lett 57:125–130. doi:10.1016/0304-3940(85)90050-3
Holmgren S, Axelsson M, Farrell AP (1992) The effect of catecholamines, substance P and vasoactive intestinal polypeptide on blood flow to the gut in the dogfish Squalus acanthias. J Exp Biol 168:161–175
Holmgren S, Fritsche R, Karila P, Gibbins IG, Axelsson M, Franklin C et al (1994) Neuropeptides in the australian lungfish Neoceratodus forsteri: effect in vivo and presence in autonomic nerves. Am J Physiol 266:R1568–R1577
Holzer P, Lippe ITH, Jocic M, Wachter CH, Erb R, Heinemann A (1993) Nitric oxide-dependent and -independent hyperamia due to calcitonin gene-related peptide in the rat stomach. Br J Pharmacol 110:404–410
Hoover DB, Hossler FE (1993) Vasoconstrictor and dilator responses to neurokinin A in isolated guinea pig heart. Peptides 14:29–36. doi:10.1016/0196-9781(93)90007-4
Hosaka K, Rayner SE, von der Weid PY, Zhao J, Imtiaz MS, van Helden DF (2006) Calcitonin gene-related peptide activates different signaling pathways in mesenteric lymphatics of guinea pigs. Am J Physiol 290:H813–H822
Jennings BL, Bell JD, Hyodo S, Toop T, Donald JA (2007) Mechanisms of vasodilation in the dorsal aorta of the elephant fish, Callorhinchus milii (Chimaeriformes: Holocephali). J Comp Physiol [B] 177:557–567
Jensen J, Conlon JM (1992) Substance-P-related and neurokinin-A-related peptides from the brain of the cod and trout. Eur J Biochem 206:659–664. doi:10.1111/j.1432-1033.1992.tb16971.x
Jensen J, Axelsson M, Holmgren S (1991) Effects of substance P and vasoactive intestinal polypeptide on gastrointestinal blood flow in the Atlantic cod, Gadus morhua. J Exp Biol 156:361–373
Jin C, Naruse S, Kitagawa M, Ishigura H, Nakajima M, Mizuno N et al (2001) The effect of calcitonin gene-related peptide on pancreatic blood flow and secretion in conscious dogs. Regul Pept 99:9–15. doi:10.1016/S0167-0115(01)00214-2
Johnsson M, Axelsson M, Holmgren S (2001) Large veins in the Atlantic cod (Gadus morhua) and the rainbow trout (Oncorhynchus mykiss) are innervated by neuropeptide containing nerves. Anat Embryol (Berl) 204:109–115. doi:10.1007/s004290100182
Karila P, Axelsson M, Franklin CE, Fritsche R, Gibbins IL, Grigg GC et al (1995) Neuropeptide immunoreactivity and co-existence in cardiovascular nerves and autonomic ganglia of the estuarine crocodile, Crocodylus porosus, and cardiovascular effects of neuropeptides. Regul Pept 58:25–39. doi:10.1016/0167-0115(95)00055-G
Karila P, Shahbazi F, Jörgen J, Holmgren S (1998) Projections and actions of tachykininergic, cholinergic, and serotonergic neurones in the intestine of the Atlantic cod. Cell Tissue Res 291:403–413. doi:10.1007/s004410051010
Kline LW, Kaneko T, Chiu KW, Harvey S, Pang PKT (1988) Calcitonin gene-related peptide in the bullfrog, Rana catesbeiana: lacalization and vascular actions. Gen Comp Endocrinol 72:123–129. doi:10.1016/0016-6480(88)90187-6
Kågström J, Holmgren S (1998) Calcitonin gene-related peptide (CGRP), but not tachykinins, cause relaxation of small arteries from the rainbow trout gut. Peptides 19:577–584. doi:10.1016/S0196-9781(97)00456-7
Kågström J, Holmgren S, Olson KR, Conlon JM, Jensen J (1996) Vasoconstrictive effects of native tachykinins in the rainbow trout, Oncorhynchus mykiss. Peptides 17:39–45. doi:10.1016/0196-9781(95)02065-9
Kågström J, Olsson C, Axelsson M, Franklin CE (1998) Peptidergic control of gastrointestinal blood flow in the estuarine crocodile, Crocodylus porosus. Am J Physiol 274:R1740–R1750
Le Mével JC, Lancien F, Mimassi N, Conlon JM (2007) Ventilatory and cardiovascular actions of centrally administered trout tachykinins in the unanesthetized trout. J Exp Biol 210:3301–3310. doi:10.1242/jeb.006106
Lundberg JM (1996) Pharmacology of cotransmission in the autonomic nervous system: integrative aspects on amines, neuropeptides, adenosine triphosphate, amino acids and the nitric oxide. Pharmacol Rev 48:113–178
Lundgaard A, Aalkjaer C, Bjurholm A, Mulvany MJ, Hansen ES (1997) Vasorelaxation in isolated bone arteries. Acta Orthop Scand 68:481–489
Maggi CA (1996) Tachykinins in the autonomic nervous system. Pharmacol Res 33:161–170. doi:10.1006/phrs.1996.0023
Moore RM, Sedrish SA, Holmes EP, Koch CE, Venugopal CS (2005) Role of endothelium and nitric oxide in modulating in vitro responses of colonic arterial and venous rings to vasodilatory neuropeptides in horses. Can J Vet Res 69:116–122
Mulvany MJ, Halpern W (1977) Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res 41:19–26
Pennefather JN, Lecci A, Candenas ML, Patak E, Pinto FM, Maggi CA (2004) Tachykinins and tachykinin receptors: a growing family. Life Sci 74:1445–1463. doi:10.1016/j.lfs.2003.09.039
Pernow B (1983) Substance P. Pharmacol Rev 35:85–141
Sann H, Friedrich R, Pierau FK (1996) Substance P and calcitonin gene-related peptide in the chicken skin: distribution and cardiovascular effects. Neuropeptides 30:273–281. doi:10.1016/S0143-4179(96)90073-6
Severini C, Improta G, Falconieri-Erspamer G, Salvadori S, Erspamer V (2002) The tachykinin peptide family. Pharmacol Rev 54:285–322. doi:10.1124/pr.54.2.285
Shahbazi F, Karila P, Olsson C, Holmgren S, Conlon JM, Jensen J (1998) Primary structure, distribution, and effects on motility of CGRP in the intestine of the cod Gadus morhua. Am J Physiol 275:R19–R28
Shahbazi F, Conlon JM, Holmgren S, Jensen J (2001) Effects of cod bradykinin and its analogs on vascular and intestinal smooth muscle of the Atlantic cod, Gadus morhua. Peptides 22:1023–1029. doi:10.1016/S0196-9781(01)00420-X
Skov PV, Bennett MB (2004) Structural basis for control of secondary vessels in the long-finned eel Anguilla reinhardtii. J Exp Biol 207:3339–3348. doi:10.1242/jeb.01164
Waugh D, Wang YX, Hazon N, Balment RJ, Conlon JM (1993) Primary structures and biological activities of substance P-related peptides from the brain of the dogfish, Scyliorhinus canicula. Eur J Biochem 214:469–474. doi:10.1111/j.1432-1033.1993.tb17943.x
Acknowledgements
We would like to thank Mrs. Christina Hagström for expert technical assistance. This work was supported by the Swedish Science Council.
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Shahbazi, F., Holmgren, S. & Jensen, J. Cod CGRP and tachykinins in coeliac artery innervation of the Atlantic cod, Gadus morhua: presence and vasoactivity. Fish Physiol Biochem 35, 369–376 (2009). https://doi.org/10.1007/s10695-008-9257-7
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DOI: https://doi.org/10.1007/s10695-008-9257-7
Keywords
- Immunohistochemistry
- In vitro pharmacology
- NKA
- Substance P
- Teleost fish