Abstract
The co-localisation of neuronal nitric oxide synthase and endothelin-1 was studied in the rat supraoptic nucleus at the electron microscopy level. Double pre-embedding immunocytochemistry was performed using ExtrAvidin-horseradish peroxidase and immunogold–silver techniques. Immunoreactivities to neuronal nitric oxide synthase and endothelin-1 were co-localised in sub-populations of endocrine neurones (cell bodies) and dendrites. Double-labelled axon terminals making asymmetrical synapses on unlabelled dendrites were also observed. The findings are discussed in terms of the possible role and significance of nitric oxide and endothlin-1 in the hypothalamo-neurohypophysial system.
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Arai H, Hori S, Aramori L, Ohkubo H, Nakanishi S (1990) Cloning and expression of cDNA encoding an endothelin receptor. Nature 348: 730–732.
Armstong WE (1995) Morphological and electrophysiological classification of hypothalamic supraoptic neurons. Prog Neurobiol 47: 91–339.
Bredt DS, Hwang PM, Snyder SH (1990) Localization of nitric oxide synthase indicating a neuronal role for nitric oxide. Nature 347: 768–770.
Bruni JE, Perumal PM (1984) Cytoarchitecture of the rats' supraoptic nucleus. Anat Embryol 170: 129–138.
Buller KM, Khanna S, Sibbald JR, Day TA (1996) Central noradrenergic neurons signal viaATP to elicit vasopressin responses to haemorrhage. Neuroscience 73: 637–642.
Cao W, Kuwaki T, Unekawa M, Ling G, Terui N, Kumada M (1993) Action of endothelin-1 on vasomotor neurons in rat rostral ventrolateral medulla. J Cardiovasc Pharmacol 22(Suppl. 8): S196–S198.
Costa A, Nappi RE, Polatti F, Poma A, Grossman AB, Nappi G (2000) Stimulating effect of HIV-1 coat protein gp120 on corticotropinreleasing hormone and arginine vasopressin in the rat hypothalamus: Involvement of nitric oxide. Exp Neurol 166: 376–384.
Cunningham Jr ET, Sawchenko PE (1988) Anatomical specificity of Noradrenergic inputs to the paraventricular and supraoptic nuclei of the rat hypothalamus. J Comp Neurol 274: 60–76.
Förstermann U, Schmidt HHHW, Pollock JS, Sheng H, Mitchell JA, Warner TD, Nakane M, Murad F (1991) Isoforms of nitric oxide synthase. Characterization and purification from different cell types. Biochem Pharmacol 42: 1849–1857.
Furchgott RF, Khan MT, Jothianandan D (1987) Evidence supporting the proposal that endothelium-derived relaxing factor is nitric oxide. Thromb Res (Suppl. 7), 5.
Gajkowska B, Viron A (1997) Protracted elevation of endothelin immunoreactivity in hypothalamo-neurohypophysial system after ischaemia. Folia Neuropathol 35:107–114.
Garthwaite J (1993) Nitric oxide signalling in the nervous system. Sem Neurosci 5: 171–180.
Giad A, Gibson SJ, Ibrahim NBN, Legon S, Bloom SR, Yanagisawa M, Varndell IM, Polak JM (1989) Endothelin 1, an endothelium-derived peptide, is expressed in neurones of the human spinal cord and dorsal root ganglia. Proc Natl Acad Sci USA 86: 7634–7638.
Hemsen A, Lundberg JM (1991) Presence of endothelin-1 and endothelin-3 in peripheral tissues and central nervous system of the pig. Regul Pept 36: 71–83.
Horowitz MJ, Bloch KD, Kim NB, Amico JA (1994) Expression of the endothelin-1 and oxytocin genes in the hypothalamus of the pregnant rat. Brain Res 648: 59–64.
Hoyle CHV, Burnstock G (1995) Criteria for defining enteric neurotransmitters. In: Gaginella TS, ed. Handbook of Methods in Gastrointestinal Pharmacology, Boca Raton, FL: CRC Press, pp. 123–140.
Ignarro LJ, Bugas GM, Wood KS, Byrns RE, Chaudhuri G (1987) Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84: 9265–9269.
Knuepfer MM, O'brien D, Hoang D, Gan Q, Song C (1994) Central sympathetic control of spinal endothelin release in the rat. Eur J Pharmacol 259: 305–308.
Krsmmanovic LZ, Stojilkovic SS, Balla T, Al-Damluji S, Weiner RI, Catt KJ (1991) Receptors and neurosecretory actions of endothelin in hypothalamic neurons. Proc Natl Acad Sci USA 88: 11124–11128.
Kurokawa K, Yamada H, Liu Y, Kudo M (2000) Immunohistochemical distribution of the endothelin-converting enzyme-1 in the rat hypothalamo-pituitary axis. Neurosci Lett 284: 81–84.
Lee M, De La Monte S, Ng S, Block K, Quertermous T (1990) Expression of the potent vasoconstrictor endothelin in the human central nervous system. J Clin Invest 86: 141–147.
Leranth C, Zaborszky L, Marton J, Palkovitz M(1975) Quantitative studies on the supraoptic nucleus in the rat. I. Synaptic organization. Exp Brain Res 22: 509–523
Lincoln J, Hoyle Chv, Burnstock G (1997) In: Lucy JA, ed. Nitric Oxide in Health and Disease. Cambridge: Cambridge University Press.
Lumme A, Vanhatalo S, Sadeniemi M, Soinila S (1997) Expression of nitric oxide synthase in hypothalamic nuclei following axonal injury or colchicine treatment. Exp Neurol 144: 248–257.
Milner P, Loesch A, Burnstock G (2000) Neural endothelin in hypertension: Increased expression in ganglion and nerves to cerebral arteries of the spontaneously hypertensive rat. J Vasc Res 37: 39–49.
Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev 43: 109–142.
Mosqueda-Garcia R, Stainback R, Fernandez-Violante R, Hamakubo T (1995) Cardiovascular effects of endothelin injected into brain nuclei regulating vasopressin release. J Cardiovasc Pharmacol 26(Suppl. 3): S159–S162.
Nakamura S, Naruse M, Naruse K, Shioda S, Nakai Y, Uemura H (1993) Colocalization of immunoreactive endothelin-1 and neurohypophysial hormones in the axons of the neural lobe of the rat. Endocrinology 132: 530–533.
Ng YK, Xue YD, Wong PT (1999) Different distributions of nitric oxide synthase-containing neurons in the mouse and rat hypothalamus. Nitric Oxide 3: 383–392.
Okere CO, Higuchi T (1996) Down-regulation of endogenous nitric oxide synthase in late-pregnancy and parturition in the rat hypothalamic magnocellular neurons and neurohypophysis. Neurosci Lett 220: 133–136.
Otukonyong EE, Okere CO, Johnstone LE, Murata T, Kaba H, Higuchi T (2000) Effect of suckling on NADPH-diaphorase (nitric oxide synthase, NOS) reactivity and NOS gene expression in the paraventricular and supraoptic nuclei of lactating rats. J Neuroendocrinol 12: 1001–1008.
Ozaki M, Shibuya I, Kabashima N, Isse T, Noguchi J, Ueta Y, Inoue Y, Shigematsu A, Yamashita H (2000) Preferential potentiation by nitric oxide of spontaneous inhibitory postsynaptic currents in rat supraoptic neurones. J Neuroendocrinol 12: 273–281.
Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524–526.
Palmer RMJ, Ashton DS, Moncada S (1988) Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333: 664–666.
Ralevic V, Burnstock G (1995) Neuropeptides in blood pressure control. In: Laragh JH & Brenner BM, eds. Hypertension: Physiology, Diagnosis and Management, New York: Raven Press Ltd, pp. 801–831.
Reid IA (1994) Role of nitric oxide in the regulation of renin and vasopressin secretion. Front Neuroendocrinol 15: 351–358.
Rettori V, Canteros G, Mccann SM (1997) Interaction between NO and oxytocin: Influence on LHRH release. Braz J Med Biol Res 30: 453–457.
Rossi NF, Chen H (2001) PVN lesions prevent the endothelin 1-induced increase in arterial pressure and vasopressin Am J Physiol 280: E349–E356.
Rubino A, Loesch A, Burnstock A (1999) Nitric oxide and endothelin-1 in coronary and pulmonary circulation. Int Rev Cytol 189: 69–93.
Serino R, Ueta Y, Tokunaga M, Hara Y, Nomura M, Kabashima N, Shibuya I, Hattori Y, Yamashita H (1998) Upregulation of hypothalamic nitric oxide synthase gene expression in streptozotocin-induced diabetic rats. Diabetologia 41: 640–648.
Shibuya I, Tanaka K, Hattori Y, Uezono Y, Harayama N, Noguchi J, Ueta Y, Izumi F, Yamashita H (1999) Evidence that multiple P2X2 purinoceptors are functionally expressed in rat supraoptic neurones. J Physiol 514: 351–367.
Snyder SH, Bredt DS (1992) Biological roles of nitric oxide. Sci Am 266: 28–35.
Sperlágh B, Sershen H, Lajtha A, Vizi ES (1998) Co-release of endogenous ATP and [3H]noradrenaline from rat hypothalamic slices: Origin and modulation by α2-adrenoceptors. Neuroscience 82: 511–520.
Stern JE, Ludwig M (2001) NO inhibits supraoptic oxytocin and vasopressin neurons via activation of GABAergic synaptic inputs. Am J Physiol Regul Integr Comp Physiol 280: R1815–R1822.
Tasaka K, Kitazumi K (1994) The control of endothelin-1 secretion. Gen Pharmacol 25: 1059–1069.
Theodosis DT, El Majdoubi M, Pierre K, Poulain DA (1998) Factors governing activity-dependent structural plasticity of the hypothalamoneurohypophysial system. Cell Mol Neurobiol 18: 285–298.
Uemura H, Naruse M, Nakamura S, Naruse K, Yamamoto T, Demura H, Hirohama T (1994) Immunoreactive endotheli-1 in the neural lobe of the rat pituitary following hemorrhage and dehydration. Endocr J 41: 685–691.
Vanhatalo S, Soinila S (1995) Nitric oxide synthase in the hypothalamopituitary pathways. J Chem Neuroanat 8: 165–173.
Vanhoutte PM (2000) Say NO to ET. J Auton Nerv Syst 81: 271–277.
Vincent S (1992) Histochemical mapping of nitric oxide synthase in the rat brain. Neuroscience 46: 755–784.
Wall KM, Ferguson AV (1992) Endothelin acts at the subfornical organ to influence the activity of putative vasopressin and oxytocin-secreting neurons. Brain Res 586: 111–116.
Wang H, Morris JF (1999) Effects of oestrogen upon nitric oxide synthase NADPH-diaphorase activity in the hypothalamo-neurohypophysial system of the rat. Neuroscience 88: 151–158.
Yamada H, Kurokawa K (1998) Histochemical studies on endothelin and the endothelin-A receptor in the hypothalamus. J Cardiovasc Pharmacol 31(Suppl. 1): S215–S218.
Yamashita H, Yamamoto S, Inenaga K, Kannan H (1991) Endothelin-3 directly affects neurons in the anteroventral third ventricle region and supraoptic nucleus of the rat hypothalamus in vitro. J Cardiovasc Pharmacol 17(Suppl. 7): S200–S202.
Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yasaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332: 411–415.
Yasin S, Costa A, Trainer P, Windle R, Forsling MJ, Grossman A (1993) Nitric oxide modulates the release of vasopressin from rat hypothalamic explants. Endocrinology 133: 1466–1469.
Yasin S, Costa A, Navarra P, Pozzoli G, Kostoglou-Athanassiou I, Forsling MJ, Grossmann A (1994) Endothelin-1 stimulates the in vitro release of neurohypophysial hormones, but not corticotropinreleasing hormone, via ETA receptors. Neuroendocrinology 60: 553–558.
Yoshizawa T, Shinmi O, Giaid A, Yanagisawa M, Gibson SJ, Kimura S, Uchiyama Y, Polak JM, Masaki T, Kanazawa I (1990) Endothelin a novel peptide in the posterior pituitary system. Science 274: 462–464.
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Mukherjee, A.B., Loesch, A. Co-localisation of Nitric Oxide Synthase and Endothelin in the Rat Supraoptic Nucleus. Histochem J 34, 181–187 (2002). https://doi.org/10.1023/A:1020950700078
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DOI: https://doi.org/10.1023/A:1020950700078