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. 1995 Jul;115(5):828–834. doi: 10.1111/j.1476-5381.1995.tb15007.x

Cross talk between receptors mediating contraction and relaxation in the arterioles but not the dilator muscle of the rat iris.

D J Gould 1, M Vidovic 1, C E Hill 1
PMCID: PMC1908528  PMID: 8548183

Abstract

1. Sympathetic nerve stimulation causes contraction of the dilator muscle and the large arterioles of the iris via the activation of alpha 1B-adrenoceptors. We have investigated whether increases in adenosine 3': 5'-cyclic monophosphate (cyclic AMP) and the activation of receptors in these tissues can modulate these nerve-mediated contractions. 2. Increasing intracellular cyclic AMP with dibutyryl cyclic AMP (1 mM), forskolin (50 microM) or isobutylmethylxanthine (100 microM) produced relaxation of both the dilator and the arterioles, abolished the nerve-mediated constriction of the arterioles, but potentiated the nerve-mediated contraction of the iris dilator. 3. Pretreatment of the preparations with cholera toxin, to activate Gs permanently, caused a dilatation of the arterioles and abolished the nerve-mediated constriction but had no effect on the dilator muscle. 4. The beta-adrenoceptor agonist, isoprenaline (1 microM), the adenosine-A1,-A2 agonist, N-ethylcarboxamidoadenosine NECA (100 nM), in the presence of the A1-selective antagonist, 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX, 10 nM), and calcitonin gene-related peptide (CGRP, 10 nM) all separately caused a dilatation of the arterioles and abolished the nerve-mediated constriction, while only isoprenaline (1 microM) produced an effect on the dilator, i.e. a relaxation but a potentiation of the nerve-mediated contraction. These results suggest the presence of at least 3 types of receptor linked to Gs and an increase in cyclic AMP in the arterioles, i.e. beta-adrenoceptor, adenosine-A2 and CGRP, but only 1 Gs-linked receptor, i.e. beta-adrenoceptors, on the dilator muscle cells.2+ '

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Selected References

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  1. Abdel-Latif A. A. Biochemical and functional interactions between the inositol 1,4,5-trisphosphate-Ca2+ and cyclic AMP signalling systems in smooth muscle. Cell Signal. 1991;3(5):371–385. doi: 10.1016/0898-6568(91)90068-6. [DOI] [PubMed] [Google Scholar]
  2. Abdel-Latif A. A. Calcium-mobilizing receptors, polyphosphoinositides, generation of second messengers and contraction in the mammalian iris smooth muscle: historical perspectives and current status. Life Sci. 1989;45(9):757–786. doi: 10.1016/0024-3205(89)90170-7. [DOI] [PubMed] [Google Scholar]
  3. Alonso-Llamazares A., Zamanillo D., Fernández A., Chinchetru M. A., Calvo P. Differential expression of the alpha 1c adrenergic receptor subtype in rat tissues. Neuroreport. 1993 Sep 10;4(11):1266–1268. doi: 10.1097/00001756-199309000-00014. [DOI] [PubMed] [Google Scholar]
  4. Bredt D. S., Ferris C. D., Snyder S. H. Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification of flavin and calmodulin binding sites. J Biol Chem. 1992 Jun 5;267(16):10976–10981. [PubMed] [Google Scholar]
  5. Burnstock G. The fifth Heymans memorial lecture-Ghent, February 17, 1990. Co-transmission. Arch Int Pharmacodyn Ther. 1990 Mar-Apr;304:7–33. [PubMed] [Google Scholar]
  6. Bültmann R., Starke K. Chloroethylclonidine: an irreversible agonist at prejunctional alpha 2-adrenoceptors in rat vas deferens. Br J Pharmacol. 1993 Feb;108(2):336–341. doi: 10.1111/j.1476-5381.1993.tb12806.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cassel D., Selinger Z. Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3307–3311. doi: 10.1073/pnas.74.8.3307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Collis M. G., Jacobson K. A., Tomkins D. M. Apparent affinity of some 8-phenyl-substituted xanthines at adenosine receptors in guinea-pig aorta and atria. Br J Pharmacol. 1987 Sep;92(1):69–75. doi: 10.1111/j.1476-5381.1987.tb11297.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ford A. P., Williams T. J., Blue D. R., Clarke D. E. Alpha 1-adrenoceptor classification: sharpening Occam's razor. Trends Pharmacol Sci. 1994 Jun;15(6):167–170. doi: 10.1016/0165-6147(94)90136-8. [DOI] [PubMed] [Google Scholar]
  10. Fuder H., Muth U. ATP and endogenous agonists inhibit evoked [3H]-noradrenaline release in rat iris via A1 and P2y-like purinoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1993 Oct;348(4):352–357. doi: 10.1007/BF00171333. [DOI] [PubMed] [Google Scholar]
  11. Gould D. J., Hill C. E. Alpha 1B-receptors and intracellular calcium mediate sympathetic nerve induced constriction of rat irideal blood vessels. J Auton Nerv Syst. 1994 Dec 15;50(2):139–150. doi: 10.1016/0165-1838(94)90004-3. [DOI] [PubMed] [Google Scholar]
  12. Gray D. W., Marshall I. Human alpha-calcitonin gene-related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide. Br J Pharmacol. 1992 Nov;107(3):691–696. doi: 10.1111/j.1476-5381.1992.tb14508.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gray D. W., Marshall I. Novel signal transduction pathway mediating endothelium-dependent beta-adrenoceptor vasorelaxation in rat thoracic aorta. Br J Pharmacol. 1992 Nov;107(3):684–690. doi: 10.1111/j.1476-5381.1992.tb14507.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gustafsson L. E., Wiklund N. P. Adenosine-modulation of cholinergic and non-adrenergic non-cholinergic neurotransmission in the rabbit iris sphincter. Br J Pharmacol. 1986 May;88(1):197–204. doi: 10.1111/j.1476-5381.1986.tb09487.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Han C., Abel P. W., Minneman K. P. Alpha 1-adrenoceptor subtypes linked to different mechanisms for increasing intracellular Ca2+ in smooth muscle. Nature. 1987 Sep 24;329(6137):333–335. doi: 10.1038/329333a0. [DOI] [PubMed] [Google Scholar]
  16. Han S. P., Naes L., Westfall T. C. Calcitonin gene-related peptide is the endogenous mediator of nonadrenergic-noncholinergic vasodilation in rat mesentery. J Pharmacol Exp Ther. 1990 Nov;255(2):423–428. [PubMed] [Google Scholar]
  17. Hill C. E., Klemm M., Edwards F. R., Hirst G. D. Sympathetic transmission to the dilator muscle of the rat iris. J Auton Nerv Syst. 1993 Nov;45(2):107–123. doi: 10.1016/0165-1838(93)90123-c. [DOI] [PubMed] [Google Scholar]
  18. Hirata Y., Takagi Y., Takata S., Fukuda Y., Yoshimi H., Fujita T. Calcitonin gene-related peptide receptor in cultured vascular smooth muscle and endothelial cells. Biochem Biophys Res Commun. 1988 Mar 30;151(3):1113–1121. doi: 10.1016/s0006-291x(88)80481-9. [DOI] [PubMed] [Google Scholar]
  19. Holzer P. Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev. 1991 Jun;43(2):143–201. [PubMed] [Google Scholar]
  20. Kubota M., Moseley J. M., Butera L., Dusting G. J., MacDonald P. S., Martin T. J. Calcitonin gene-related peptide stimulates cyclic AMP formation in rat aortic smooth muscle cells. Biochem Biophys Res Commun. 1985 Oct 15;132(1):88–94. doi: 10.1016/0006-291x(85)90992-1. [DOI] [PubMed] [Google Scholar]
  21. Lincoln T. M., Fisher-Simpson V. A comparison of the effects of forskolin and nitroprusside on cyclic nucleotides and relaxation in the rat aorta. Eur J Pharmacol. 1984 May 18;101(1-2):17–27. doi: 10.1016/0014-2999(84)90026-8. [DOI] [PubMed] [Google Scholar]
  22. Lomasney J. W., Cotecchia S., Lefkowitz R. J., Caron M. G. Molecular biology of alpha-adrenergic receptors: implications for receptor classification and for structure-function relationships. Biochim Biophys Acta. 1991 Oct 26;1095(2):127–139. doi: 10.1016/0167-4889(91)90075-9. [DOI] [PubMed] [Google Scholar]
  23. Lomasney J. W., Cotecchia S., Lorenz W., Leung W. Y., Schwinn D. A., Yang-Feng T. L., Brownstein M., Lefkowitz R. J., Caron M. G. Molecular cloning and expression of the cDNA for the alpha 1A-adrenergic receptor. The gene for which is located on human chromosome 5. J Biol Chem. 1991 Apr 5;266(10):6365–6369. [PubMed] [Google Scholar]
  24. Manolopoulos V. G., Pipili-Synetos E., Den Hertog A., Nelemans A. Inositol phosphates formed in rat aorta after alpha 1-adrenoceptor stimulation are inhibited by forskolin. Eur J Pharmacol. 1991 May 25;207(1):29–36. doi: 10.1016/s0922-4106(05)80034-3. [DOI] [PubMed] [Google Scholar]
  25. Maynard K. I., Saville V. L., Burnstock G. Sensory-motor neuromodulation of sympathetic vasoconstriction in the rabbit central ear artery. Eur J Pharmacol. 1990 Oct 9;187(2):171–182. doi: 10.1016/0014-2999(90)90004-p. [DOI] [PubMed] [Google Scholar]
  26. Medgett I. C. Modulation of transmission in rat sympathetic ganglia by activation of presynaptic alpha- and beta-adrenoceptors. Br J Pharmacol. 1983 Jan;78(1):17–27. doi: 10.1111/j.1476-5381.1983.tb09358.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Milligan G. Techniques used in the identification and analysis of function of pertussis toxin-sensitive guanine nucleotide binding proteins. Biochem J. 1988 Oct 1;255(1):1–13. doi: 10.1042/bj2550001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Murthy K. S., Severi C., Grider J. R., Makhlouf G. M. Inhibition of IP3 and IP3-dependent Ca2+ mobilization by cyclic nucleotides in isolated gastric muscle cells. Am J Physiol. 1993 May;264(5 Pt 1):G967–G974. doi: 10.1152/ajpgi.1993.264.5.G967. [DOI] [PubMed] [Google Scholar]
  29. Neild T. O. Measurement of arteriole diameter changes by analysis of television images. Blood Vessels. 1989;26(1):48–52. [PubMed] [Google Scholar]
  30. Pernow J. Actions of constrictor (NPY and endothelin) and dilator (substance P, CGRP and VIP) peptides on pig splenic and human skeletal muscle arteries: involvement of the endothelium. Br J Pharmacol. 1989 Jul;97(3):983–989. doi: 10.1111/j.1476-5381.1989.tb12040.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rhoden K. J., Barnes P. J. Potentiation of nonadrenergic neural relaxation in guinea pig airways by a cyclic cAMP phosphodiesterase inhibitor. J Pharmacol Exp Ther. 1990 Jan;252(1):396–402. [PubMed] [Google Scholar]
  32. Starke K., Göthert M., Kilbinger H. Modulation of neurotransmitter release by presynaptic autoreceptors. Physiol Rev. 1989 Jul;69(3):864–989. doi: 10.1152/physrev.1989.69.3.864. [DOI] [PubMed] [Google Scholar]
  33. Starke K., von Kügelgen I., Bulloch J. M., Illes P. Nucleotides as cotransmitters in vascular sympathetic neuroeffector transmission. Blood Vessels. 1991;28(1-3):19–26. doi: 10.1159/000158839. [DOI] [PubMed] [Google Scholar]
  34. Tachado S. D., Akhtar R. A., Abdel-Latif A. A. Activation of beta-adrenergic receptors causes stimulation of cyclic AMP, inhibition of inositol trisphosphate, and relaxation of bovine iris sphincter smooth muscle. Biochemical and functional interactions between the cyclic AMP and calcium signalling systems. Invest Ophthalmol Vis Sci. 1989 Oct;30(10):2232–2239. [PubMed] [Google Scholar]
  35. Tachado S. D., Akhtar R. A., Zhou C. J., Abdel-Latif A. A. Effects of isoproterenol and forskolin on carbachol- and fluoroaluminate-induced polyphosphoinositide hydrolysis, inositol trisphosphate production, and contraction in bovine iris sphincter smooth muscle: interaction between cAMP and IP3 second messenger systems. Cell Signal. 1992 Jan;4(1):61–75. doi: 10.1016/0898-6568(92)90008-v. [DOI] [PubMed] [Google Scholar]
  36. Takayanagi I., Shiraishi K., Kokubu N. Alpha 1B-adrenoceptor mechanisms in rabbit iris dilator. Jpn J Pharmacol. 1992 Jul;59(3):301–305. doi: 10.1254/jjp.59.301. [DOI] [PubMed] [Google Scholar]
  37. Vials A., Burnstock G. A2-purinoceptor-mediated relaxation in the guinea-pig coronary vasculature: a role for nitric oxide. Br J Pharmacol. 1993 Jun;109(2):424–429. doi: 10.1111/j.1476-5381.1993.tb13586.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Voigt M. M., Kispert J., Chin H. M. Sequence of a rat brain cDNA encoding an alpha-1B adrenergic receptor. Nucleic Acids Res. 1990 Feb 25;18(4):1053–1053. doi: 10.1093/nar/18.4.1053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wright I. K., Amirchetty-Rao S., Kendall D. A. Potentiation by forskolin of both SNP- and ANP-stimulated cyclic GMP accumulation in porcine isolated palmar lateral vein. Br J Pharmacol. 1994 Aug;112(4):1146–1150. doi: 10.1111/j.1476-5381.1994.tb13203.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. von Kügelgen I., Späth L., Starke K. Stable adenine nucleotides inhibit [3H]-noradrenaline release in rabbit brain cortex slices by direct action at presynaptic adenosine A1-receptors. Naunyn Schmiedebergs Arch Pharmacol. 1992 Aug;346(2):187–196. doi: 10.1007/BF00165300. [DOI] [PubMed] [Google Scholar]

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