Novel Challenges for the Therapeutics of Depression: Pharmacological Modulation of Interaction between the Intracellular Signaling Pathways Mediated by Ca2+ and cAMP
Article Sidebar
Main Article Content
Abstract
Depression is a psychiatric disease resulting mainly by dysfunction of serotoninergic and monoaminergic neurotransmission in central nervous system (CNS). Due to the multifaceted nature of depression and our limited understanding on its etiology, depression is difficult to be treated with currently available pharmaceuticals. Then, new therapeutic strategies for depression have been proposed. Since 1975, several clinical studies have reported that L-type Ca2+ channel blockers (CCBs), used in anti-hypertensive therapy, produce increase of plasma catecholamine levels and tachycardia, typical symptoms of sympathetic hyperactivity. Despite these adverse effects of CCBs have been initially attributed to adjust reflex of arterial pressure, during almost four decades these enigmatic phenomena remained unclear. In 2013, we discovered that this paradoxical sympathetic hyperactivity produced by CCBs results from the increase of catecholamines release from sympathetic nerves, and adrenal chromaffin cells, due to its modulatory action on the interaction between intracellular signaling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP signalling interaction). Then, the pharmacological modulation of this interaction by combined use of L-type CCBs, and cAMP-enhancer compounds, could be a more efficient (and safer) therapeutic strategy to produce increase of serotoninergic and monoaminergic neurotransmission in the CNS due to enhance of serotonin and monoamines release, thus attenuating clinical symptoms of depression in humans.
Article Details
Copyright (c) 2017 Caricati-Neto A, et al.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Caricati-Neto A, García AG, Bergantin LB. Pharmacological implications of the Ca2+/cAMP signalling interaction: from risk for antihypertensive therapy to potential beneficial for neurological and psychiatric disorders. Pharmacol Res Perspect. 2015; 3: e00181. Ref.: https://goo.gl/BBr2kt
Pytka K, Podkowa K, Rapacz A, Podkowa A, Żmudzka E, et al. The role of serotonergic, adrenergic and dopaminergic receptors in antidepressant-like effect. Pharmacol Rep. 2016; 68: 263-274. Ref.: https://goo.gl/MP8VUK
Bergantin LB, Souza CF, Ferreira RM, Smaili SS, Jurkiewicz NH, et al. Novel model for “calcium paradox” in sympathetic transmission of smooth muscles: role of cyclic AMP pathway. Cell Calcium. 2013; 54: 202-212. Ref.: https://goo.gl/NeN9ha
Bergantin LB, Jurkiewicz A, García AG, Caricati-Neto A. A Calcium Paradox in the Context of Neurotransmission. J Pharm Pharmacol. 2015; 3: 253-261. Ref.: https://goo.gl/hl07Cc
Bergantin LB, Caricati-Neto A. Challenges for the pharmacological treatment of neurological and psychiatric disorders: Implications of the Ca2+/cAMP intracellular signalling interaction. Eur J Pharmacol. 2016; 788, 255-260. Ref.: https://goo.gl/ItZfbz
Bergantin LB, Caricati-Neto A. Insight from “Calcium Paradox” due to Ca2+/cAMP Interaction: Novel Pharmacological Strategies for the Treatment of Depression. Int Arch Clin Pharmacol. 2016; 2: 2-7. Ref.: https://goo.gl/QPbmtY
Bergantin LB, Caricati-Neto A. Novel Insights for Therapy of Parkinson’s disease: Pharmacological Modulati on of the Ca2+/cAMP Signalling Interaction. Austin Neurol & Neurosci. 2016; 1: 1-4. Ref.: https://goo.gl/XkpzIH
Bergantin LB, Caricati-Neto A. Recent advances in pharmacotherapy of neurological and psychiatric disorders promoted by discovery of the role of Ca2+/cAMP signaling interaction in the neurotransmission and neuroprotection. Adv Pharmac J. 2016; 1: 66-70. Ref.: https://goo.gl/9ypgJo
Kaster MP, Moretti M, Cunha MP, Rodrigues AL (2016). Novel approaches for the management of depressive disorders. Eur J Pharmacol. 2016; 771: 236-40. Ref.: https://goo.gl/Z5fvbG
Köhler S, Cierpinsky K, Kronenberg G, Adli M . The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants. J Psychopharmacol. 2016; 30: 13-22. Ref.: https://goo.gl/nmmzva
Douglas WW, Rubin RP. The role of calcium in the secretory response of the adrenal medulla to acetylcholine. J Physiol. 1961; 159: 40-57. Ref.: https://goo.gl/9uWF59
Baker PF, Knight DE. Calcium-dependent exocytosis in bovine adrenal medullary cells with leaky plasma membranes. Nature; 1978; 276: 620-622. Ref.: https://goo.gl/ifjTU3
Chern YJ, Kim KT, Slakey LL, Westhead EW. Adenosine receptors activate adenylate cyclase and enhance secretion from bovine adrenal chromaffin cells in the presence of forskolin. J Neurochem. 1988; 50: 1484-1493. Ref.: https://goo.gl/Z25XIH
Cooper DM, Mons N, Karpen JW. Adenylyl cyclases and the interaction between calcium and cAMP signalling. Nature. 1995; 374: 421-424. Ref.: https://goo.gl/w9JkIm
Yule DI, Betzenhauser MJ, Joseph SK. Linking structure to function: recent lessons from inositol 1,4,5-trisphosphate receptor mutagenesis. Cell Calcium. 2010; 47: 469-479. Ref.: https://goo.gl/qZbaac
Ahuja M, Jha A, Maléth J, Park S, Muallem S. cAMP and Ca²⁺ signaling in secretory epithelia: crosstalk and synergism. Cell Calcium. 2014; 55: 385-93. Ref.: https://goo.gl/v5sEi7
Grossman E, Messerli FH. Effect of calcium antagonists on sympathetic activity. Eur Heart J. 1998; 19: 27-31. Ref.: https://goo.gl/3VaR2B
Kreye VA, Luth JB. Proceedings: verapamil-induced phasic contractions of the isolated rat vas deferens. Naunyn Schmiedebergs Arch Pharmacol. 1975; 287: R43. Ref.: https://goo.gl/34bQaA
French AM, Scott NC. A comparison of the effects of nifedipine and verapamil on rat vas deferens. Br J Pharmacol. 1981; 73: 321-323. Ref.: https://goo.gl/gfli14
Moritoki H, Iwamoto T, Kanaya J, Maeshiba Y, Ishida Y, et al. Verapamil enhances the non-adrenergic twitch response of rat vas deferens. Eur J Pharmacol. 1987; 140: 75-83. Ref.: https://goo.gl/0yeqf1
Prakhie IV, Oxenkrug GF. The effect of nifedipine, Ca(2+) antagonist, on activity of MAO inhibitors, N-acetylserotonin and melatonin in the mouse tail suspension test. Int J Neuropsychopharmacol. 1998; 1: 35-40. Ref.: https://goo.gl/qDZmkH
Ogihara T, Nakagawa M, Ishikawa H, Mikami H, Takeda K, et al. Effect of manidipine, a novel calcium channel blocker, on quality of life in hypertensive patients. Blood Press Suppl. 1992; 3: 135-139. Ref.: https://goo.gl/OCWfvh
Veng LM, Mesches MH, Browning MD. Age-related working memory impairment is correlated with increases in the L-type calcium channel protein α1D (Cav1.3) in area CA1 of the hippocampus and both are ameliorated by chronic nimodipine treatment. Brain Res Mol Brain Res. 2003; 110: 193-202. Ref.: https://goo.gl/J1Igy5
Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, et al. ‘Rejuvenation’ protects neurons in mouse models of Parkinson’s disease. Nature. 2007; 447: 1081-1086. Ref.: https://goo.gl/d2EjVz
Tsukuda K, Mogi M, Li JM, Iwanami J, Min LJ, et al. Diabetes-associated cognitive impairment is improved by a calcium channel blocker, nifedipine. Hypertension. 2008; 51: 528-533. Ref.: https://goo.gl/zgud8g
Sommer N, Loschmann PA, Northoff GH, Weller M, Steinbrecher A, et al. The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis. Nat Med. 1995; 1: 244-248. Ref.: https://goo.gl/eXv7C8
Li YF, Cheng YF, Huang Y, Conti M, et al. Phosphodiesterase-4D knock-out and RNA interference-mediated knock-down enhance memory and increase hippocampal neurogenesis via increased cAMP signaling. J Neurosci. 2011; 31: 172-183. Ref.: https://goo.gl/fCsYtf
Xiao L, O'Callaghan JP, O'Donnell JM. Effects of repeated treatment with phosphodiesterase-4 inhibitors on cAMP signaling, hippocampal cell proliferation, and behavior in the forced-swim test. J Pharmacol Exp Ther. 2011; 338: 641-647. Ref.: https://goo.gl/myAhrx
De Vry J, Fritze J, Post R. The management of coexisting depression in patients with dementia: potential of calcium channel antagonists. Clinical Neuropharmacology. 1997; 20: 22-35. Ref.: https://goo.gl/OIvzJr
Vetulani J. The action of antidepressant drugs administered during calcium channel blockade. Pol J Pharmacol. 1993; 45: 179-84. Ref.: https://goo.gl/IfGE3E
Taragano FE, Bagnatti P, Allegri RF. A double-blind, randomized clinical trial to assess the augmentation with nimodipine of antidepressant therapy in the treatment of "vascular depression". Int Psychogeriatr. 2005; 17: 487-498. Ref.: https://goo.gl/19kry3