Author(s): Shalinee Soni, Lokesh Verma


DOI: 10.52711/0974-360X.2024.00407   

Address: Shalinee Soni1*, Lokesh Verma2
1Research Scholar, Department of Pharmacology, Sanjeev Agrawal Global Educational University, Bhopal 462022, Madhya Pradesh, India.
2Associate Professor, Department of Pharmacology, Sanjeev Agrawal Global Educational University, Bhopal 462022, Madhya Pradesh, India.
*Corresponding Author

Published In:   Volume - 17,      Issue - 6,     Year - 2024

This concise review provides an update on the relationship between nicotine and neurotransmitters, focusing on the release and binding of specialized macromolecules known as neurotransmitters to specific receptors. The discussion highlights the two subtypes of the nicotinic receptor, N1 and N2, with N1 associated with muscle/peripheral functions and N2 with central/neuronal functions. The production of chemicals through nicotinic cholinergic receptors by sympathetic postganglionic neurons, adrenal chromaffin cells, and parasympathetic postganglionic neurons is examined. The presence of cholinergic receptors in both the sympathetic and parasympathetic neurons, their affinity for acetylcholine, and their relevance in obstructive lung disease are briefly addressed. The potential therapeutic impact of antimuscarinic receptor medicines for this condition is acknowledged. The review underscores the importance of bridging evolving sectors to explore the beneficial applications of nicotinic receptor ligand and emphasizes the significance of understanding nicotine receptors in various diseases.

Cite this article:
Shalinee Soni, Lokesh Verma. Nicotine and Neurotransmitters an Update. Research Journal of Pharmacy and Technology. 2024; 17(6):2605-2. doi: 10.52711/0974-360X.2024.00407

Shalinee Soni, Lokesh Verma. Nicotine and Neurotransmitters an Update. Research Journal of Pharmacy and Technology. 2024; 17(6):2605-2. doi: 10.52711/0974-360X.2024.00407   Available on:

1.    Gupta S, Kulhara P. Cellular and molecular mechanisms of drug dependence: An overview and update. Indian Journal of Psychiatry. 2007; 49(2): 85.
2.    Parri HR, Hernandez CM, Dineley KT. Research update: Alpha7 nicotinic acetylcholine receptor mechanisms in Alzheimer's disease. Biochem. Pharmacol. 2011; 82(8): 931-42.
3.    Tutka P. Vinnikov D, Courtney RJ, Benowitz NL. Cytisine for nicotine addiction treatment: a review of pharmacology, therapeutics and an update of clinical trial evidence for smoking cessation. Addiction. 2019; 114(11): 1951-69.
4.    Elrashidi MY, Ebbert JO. Emerging drugs for the treatment of tobacco dependence: 2014 update. Expert Opinion on Emerging Drugs. 2014; 19(2): 243-60.
5.    Rosy JS. E cigarette. IJANM. 2019; 7(1): 74-76.
6.    Haustein K, Krause J, Haustein H, et al. Effects of cigarette smoking or nicotine replacement on cardiovascular risk factors and parameters of haemorheology. J. Intern. Med. 2002; 252:130–9. doi: 10.1046/j.1365-2796.2002.01014.x
7.    Khandakar AM. Smoking and chewing tobacco: obstacle towards sustainable development. Res. J. Humanit Soc Sci. 2013; 4(4): 603-607.
8.    Jadhav RP, Kengar MD, Nikam NR, Bhutkar MA. Tobacco Cancer: A Review. Asian J Res Phar+ Sci. 2019; 9(4): 276-281.
9.    Chiu J, Chien S. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol Rev. 2011; 91: 327–87. doi: 10.1152/physrev.00047.2009
10.    Aveleira C, Botelho M, Cavadas C. NPY/neuropeptide Y enhances autophagy in the hypothalamus: a mechanism to delay aging? Autophagy. 2015; 11: 1431–3. doi: 10.1080/15548627.2015.1062202
11.    Peng S, Zhou Y, Song Z, Lin S. Effects of neuropeptide y on stem cells and their potential applications in disease therapy. Stem Cells Int. 2017; 2017: 6823917. doi: 10.1155/2017/6823917
12.    Yang Z, Han S, Keller M, et al. Structural basis of ligand binding modes at the neuropeptide Y Y receptor. Nature. 2018; 556: 520–524. doi: 10.1038/s41586-018-0046-x.
13.    Businaro R, Scaccia E, Bordin A, et al. Platelet lysate-derived neuropeptide y influences migration and angiogenesis of human adipose tissue-derived stromal cells. Sci Rep. 2018; 8: 14365. doi: 10.1038/s41598-018-32623-8
14.    Mormède P, Castagné V, Rivet J, Gaillard R, et al. Involvement of neuropeptide Y in neuroendocrine stress responses. Central and peripheral studies. J Neural Transm. 1990; 29: 65–75. doi: 10.1007/978-3-7091-9050-0_8
15.    Comeras L, Herzog H, Tasan R. Neuropeptides at the crossroad of fear and hunger: a special focus on neuropeptide Y. Ann NY Acad Sci. 2019; 1455: 59–80. doi: 10.1111/nyas.14179
16.    Chen Y, Essner R, Kosar S, et al. Sustained NPY signaling enables AgRP neurons to drive feeding. eLife. 2019; 8: e46348. doi: 10.7554/eLife.46348
17.    Cheng Y, Tang X, Li Y, et al. Depression-induced neuropeptide y secretion promotes prostate cancer growth by recruiting myeloid cells. Clin Cancer Res. 2019; 25: 2621–32. doi: 10.1158/1078-0432.Ccr-18-2912
18.    Mahadeva Rao US, Yusoff HBM. Unraveling the association of tobacco smoking (nicotine) with gut and adipocyte appetite regulator hormones – a systematic review. Res. J. Pharm. Technol. 2019; 12(2): 913-919.
19.    Park IS, Yun HK. Factors associated with smoking frequency among intermittent smokers focused on male adolescents. Res. J. Pharm. Technol. 2017; 10(7): 2345-2349.
20.    Reichmann F, Holzer P. Neuropeptide Y: a stressful review. Neuropeptides. 2016; 55: 99–109. doi: 10.1016/j.npep.2015.09.008
21.    Hassan A, Mancano G, Kashofer K, et al. High-fat diet induces depression-like behaviour in mice associated with changes in microbiome, neuropeptide Y, and brain metabolome. Nutri Neurosci. 2019; 22: 877–93. doi: 10.1080/1028415x.2018.1465713
22.    Imai Y, Patel H, Hawkins E, et al. Insulin secretion is increased in pancreatic islets of neuropeptide Y-deficient mice. Endocrinology. 2007; 148: 5716–23. doi: 10.1210/en.2007-0404
23.    Yu J, Loh K, Song Z, et al. Update on glycerol-3-phosphate acyltransferases: the roles in the development of insulin resistance. Nutrit Diab. 2018; 8: 34. doi: 10.1038/s41387-018-0045-x
24.    Chen Z, Feng G, Nishiwaki K, et al. Possible roles of neuropeptide Y Y3-receptor subtype in rat aortic endothelial cell proliferation under hypoxia, and its specific signal transduction. Am J Physiol Heart Circul Physiol. 2007; 293: H959–67. doi: 10.1152/ajpheart.00886.2006
25.    Qiu J, Bosch M, Zhang C, et al. Estradiol protects neuropeptide y/agouti-related peptide neurons against insulin resistance in females. Neuroendocrinology. 2020; 110: 105–18. doi: 10.1159/000501560
26.    Donoso M, Miranda R, Irarrázaval M, Huidobro-Toro J. Neuropeptide Y is released from human mammary and radial vascular biopsies and is a functional modulator of sympathetic cotransmission. J. Vasc Res. 2004; 41: 387–99. doi: 10.1159/000080900
27.    Lagraauw H, Westra M, Bot M, et al. Vascular neuropeptide Y contributes to atherosclerotic plaque progression and perivascular mast cell activation. Atherosclerosis. 2014; 235: 196–203. doi: 10.1016/j.atherosclerosis.2014.04.025
28.    Wu W, Peng S, Shi Y, et al. NPY promotes macrophage migration by upregulating matrix metalloproteinase-8 expression. J Cell Physiol. 2020; 236: 1903–12. doi: 10.1002/jcp.29973
29.    Robich M, Matyal R, Chu L, et al. Effects of neuropeptide Y on collateral development in a swine model of chronic myocardial ischemia. J. Mol Cell Cardiol. 2010; 49: 1022–30. doi: 10.1016/j.yjmcc.2010.08.022
30.    Thorsell A, Slawecki C, El Khoury A, et al. The effects of social isolation on neuropeptide Y levels, exploratory and anxiety-related behaviors in rats. Pharmacol Biochem Behav. 2006; 83: 28–34. doi: 10.1016/j.pbb.2005.12.005
31.    Hoirisch-Clapauch S. Anxiety-related bleeding and thrombosis. Sem Thromb Hemost. 2018; 44: 656–61. doi: 10.1055/s-0038-1639501
32.    Rojas J, Stafford J, Saadat S, et al. Central nervous system neuropeptide Y signaling via the Y1 receptor partially dissociates feeding behavior from lipoprotein metabolism in lean rats. Am J Physiol Endocrinol Metab. 2012; 303: E1479–88. doi: 10.1152/ajpendo.00351.2012
33.    Cho Y, Kim C. Neuropeptide Y promotes beta-cell replication via extracellular signal-regulated kinase activation. Biochem Biophys Res Commun. 2004; 314: 773–80. doi: 10.1016/j.bbrc.2003.12.170
34.    Kulkarni R, Wang Z, Wang R, et al. Glibenclamide but not other sulphonylureas stimulates release of neuropeptide Y from perifused rat islets and hamster insulinoma cells. J Endocrinol. 2000; 165: 509–18. doi: 10.1677/joe.0.1650509
35.    Sun W, Li L, Huang X, et al. The central mechanism of risperidone-induced hyperprolactinemia. Progress Neuro-Psychopharm Biol Psychiatry. 2017; 76: 134–9. doi: 10.1016/j.pnpbp.2017.03.009
36.    Choi B, Shin M, Kim E, et al. Elevated neuropeptide y in endothelial dysfunction promotes macrophage infiltration and smooth muscle foam cell formation. Front Immunol. 2019; 10: 1701. doi: 10.3389/fimmu.2019.01701
37.    Aydin C, Oztan O, Isgor C. Vulnerability to nicotine abstinence-related social anxiety-like behavior: molecular correlates in neuropeptide Y, Y2 receptor and corticotropin releasing factor. Neurosci Lett. 2011; 490: 220–5. doi: 10.1016/j.neulet.2010.12.056
38.    Dietrich P, Moleda L, Kees F, et al. Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: impact of exogenous neuropeptide Y. J Hepatol. 2013; 58: 254–61. doi: 10.1016/j.jhep.2012.09.027
39.    Kudari A. Smoking kills: Help an individual in quit smoking; nursing consideration. Asian J. Nur. Edu. Research. 2017; 7(3): 441-446.
40.    Krishnamurthy K, Zin T, Priyamvatha K, Mahadeva Rao US, Suganya M. Detection of nicotine by a new system. Asian J. Pharm. Anal. 2022; 12(3): 179-0.
41.    Lundberg J, Franco-Cereceda A, Hemsén A, et al.. Pharmacology of noradrenaline and neuropeptide tyrosine (NPY)-mediated sympathetic cotransmission. Fund. Clin. Pharm. 1990; 4: 373–91. doi: 10.1111/j.1472-8206.1990.tb00692.x
42.    Tsurumaki T, Nagai S, Bo X, et al. Potentiation by neuropeptide Y of 5HT2A receptor-mediated contraction in porcine coronary artery. Europ J. Pharm. 2006; 544: 111–7. doi: 10.1016/j.ejphar.2006.06.036
43.    Hubers S, Wilson J, Yu C, et al. DPP (Dipeptidyl Peptidase)-4 inhibition potentiates the vasoconstrictor response to NPY (Neuropeptide Y) in humans during renin-angiotensin-aldosterone system inhibition. Hypertension. 2018; 72: 712–9. doi: 10.1161/hypertensionaha.118.11498
44.    Movafagh S, Hobson J, Spiegel S, et al. Neuropeptide Y induces migration, proliferation, and tube formation of endothelial cells bimodally via Y1, Y2, and Y5 receptors. FASEB J. 2006; 20: 1924–6. doi: 10.1096/fj.05-4770fje
45.    Eshun D, Saraf R, Bae S, et al. Neuropeptide Y incorporated into PVAX nanoparticle improves functional blood flow in a murine model of hind limb ischemia. J Appl Physiol. 2017; 122: 1388–97. doi: 10.1152/japplphysiol.00467.2016
46.    Koli MR, Girase CJ, Patil PA. Scientific approach to treat tobacco addiction – a review. Res. J. Pharmacogn Phytochem. 2020; 12(4): 231-234.
47.    Zukowska-Grojec Z, Karwatowska-Prokopczuk E, Rose W, et al. Neuropeptide Y: a novel angiogenic factor from the sympathetic nerves and endothelium. Circul. Res. 1998; 83: 187–95. doi: 10.1161/01.res.83.2.187
48.    Ribatti D, Conconi M, Nussdorfer G. Nonclassic endogenous novel [corrected] regulators of angiogenesis. Pharmacol. Rev. 2007; 59: 185–205. doi: 10.1124/pr.59.2.3
49.    Klinjampa R, Sitticharoon C, Souvannavong-Vilivong X, Sripong C, Keadkraichaiwat I, Churintaraphan M, et al. Placental Neuropeptide Y (NPY) and NPY receptors expressions and serum NPY levels in preeclampsia. Exp Biol Med. 2019; 244: 380–8. doi: 10.1177/1535370219831437
50.    Zhu P, Sun W, Zhang C, et al. The role of neuropeptide Y in the pathophysiology of atherosclerotic cardiovascular disease. Int. J. Cardiol. 2016; 220: 235–41. doi: 10.1016/j.ijcard.2016.06.138
51.    Grundemar L, Håkanson R. Neuropeptide Y effector systems: perspectives for drug development. Trends Pharm. Sci. 1994; 15: 153–9. doi: 10.1016/0165-6147(94)90076-0
52.    Zhou J, Zhang L, Wei H, et al. Neuropeptide Y induces secretion of high-mobility group box 1 protein in mouse macrophage via PKC/ERK dependent pathway. J Neuroimmunol. 2013; 260: 55–9. doi: 10.1016/j.jneuroim.2013.04.005
53.    Zaldivia M, Hering D, Marusic P, et al. Successful renal denervation decreases the platelet activation status in hypertensive patients. Cardiovasc Res. 2020; 116: 202–10. doi: 10.1093/cvr/cvz033
54.    Xue J, Scotti E, Stoffel M. CDK8 regulates insulin secretion and mediates postnatal and stress-induced expression of neuropeptides in pancreatic β cells. Cell Rep. 2019; 28: 2892–904.e7. doi: 10.1016/j.celrep.2019.08.025
55.    Long M, Zhou J, Li D, et al. Long-term over-expression of neuropeptide y in hypothalamic paraventricular nucleus contributes to adipose tissue insulin resistance partly via the Y5 receptor. PLoS ONE. 2015; 10: e0126714. doi: 10.1371/journal.pone.0126714
56.    Gomes R, Bueno F, Schamber C, et al. Maternal diet-induced obesity during suckling period programs offspring obese phenotype and hypothalamic leptin/insulin resistance. J. Nutr Biochem. 2018; 61: 24–32. doi: 10.1016/j.jnutbio.2018.07.006
57.    Ritz T, Trueba A. Airway nitric oxide and psychological processes in asthma and health: a review. Ann Allergy Asthma Immunol. 2014; 112: 302–8. doi: 10.1016/j.anai.2013.11.022
58.    Yue Y, Xu D, Wang Y, et al. Effect of inducible nitric oxide synthase and neuropeptide Y in plasma and placentas from intrahepatic cholestasis of pregnancy. J. Obstetr Gynaecol Res. 2018; 44: 1377–383. doi: 10.1111/jog.13681
59.    Patle P, Tenpe C, Rathod S, Gautam D. Effect 1 of NMDA receptor agonist and antagonist on nicotine withdrawal induced hyperexcitability in mice. Asian J. Res. Pharm. Sci. 2021; 11(3): 205-2.
60.    Zukowska Z, Pons J, Lee E, Li L. Neuropeptide Y: a new mediator linking sympathetic nerves, blood vessels and immune system? Can J. Physiol. Pharmacol. 2003; 81: 89–94. doi: 10.1139/y03-006
61.    Tan C, Green P, Tapoulal N, et al. The role of neuropeptide Y in cardiovascular health and disease. Front Physiol. 2018; 9: 1281. doi: 10.3389/fphys.2018.01281
62.    Huang L, Winzer-Serhan U. Nicotine regulates mRNA expression of feeding peptides in the arcuate nucleus in neonatal rat pups. Dev Neurob. 2007; 67: 363–77. doi: 10.1002/dneu.20348
63.    Hiremagalur B, Sabban E. Nicotine elicits changes in expression of adrenal catecholamine biosynthetic enzymes, neuropeptide Y and immediate early genes by injection but not continuous administration. Brain Res Molecular Brain Res. 1995; 32: 109–5. doi: 10.1016/0169-328x(95)00068-4
64.    Cavadas C, Silva A, Mosimann F, et al. NPY regulates catecholamine secretion from human adrenal chromaffin cells. J Clin Endocrinol Metab. 2001; 86: 5956–63. doi: 10.1210/jcem.86.12.8091
65.    Jahng J, Houpt T, Joh T, Wessel T. Expression of catecholamine-synthesizing enzymes, peptidylglycine alpha-amidating monooxygenase, and neuropeptide Y mRNA in the rat adrenal medulla after acute systemic nicotine. J Mol Neurosci. 1997; 8: 45–52. doi: 10.1007/bf02736862
66.    De Sousa P, Cherian G, Thomas J, Thulesius O. Coronary artery constriction is enhanced with nicotine and propranolol, particularly after endothelial damage. Clin Physiol. 1991; 11: 143–52. doi: 10.1111/j.1475-097x.1991.tb00107.x
67.    Herring N, Tapoulal N, Kalla M, et al. Neuropeptide-Y causes coronary microvascular constriction and is associated with reduced ejection fraction following ST-elevation myocardial infarction. Europ Heart J. 2019; 40: 1920–29. doi: 10.1093/eurheartj/ehz115
68.    Prieto D, Arcos L, Martínez P, et al. Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in horse penile small arteries. Br J Pharmacol. 2004; 143: 976–86. doi: 10.1038/sj.bjp.0706005
69.    Mirman B, Ikeda I, Zhang Z, et al. Effects of neuropeptide Y on the microvasculature of human skeletal muscle. Surgery. 2020; 168: 155–9. doi: 10.1016/j.surg.2020.04.020
70.    Pedrazzini T, Pralong F, Grouzmann E. Neuropeptide Y: the universal soldier. CMLS. 2003; 60: 350–77. doi: 10.1007/s000180300029
71.    Pablo Huidobro-Toro J, Verónica Donoso M. Sympathetic co-transmission: the coordinated action of ATP and noradrenaline and their modulation by neuropeptide Y in human vascular neuroeffector junctions. Europ J Pharm. 2004; 500: 27–35. doi: 10.1016/j.ejphar.2004.07.008
72.    Komaru T, Ashikawa K, Kanatsuka H, et al.. Neuropeptide Y modulates vasoconstriction in coronary microvessels in the beating canine heart. Circul Res. 1990; 67: 1142–51. doi: 10.1161/01.res.67.5.1142
73.    Woo N, Ganguly P. Altered neuropeptide Y effects on noradrenaline levels in the paraventricular nucleus of rats following aortic constriction. Can J. Cardiol. 1994; 10: 471–6.
74.    Calvillo L, Gironacci M, Crotti L, et al. Neuroimmune crosstalk in the pathophysiology of hypertension. Nat Rev Cardiol. 2019; 16: 476–90.
75.    Fabi F, Argiolas L, Ruvolo G, del Basso P. Neuropeptide Y-induced potentiation of noradrenergic vasoconstriction in the human saphenous vein: involvement of endothelium generated thromboxane. Br J. Pharm. 1998; 124: 101. doi: 10.1038/sj.bjp.0701808
76.    Stephens D, Saad A, Bennett L, et al. Neuropeptide Y antagonism reduces reflex cutaneous vasoconstriction in humans. Am J Physiol Heart Circul Physiol. 2004; 287: H1404–9. doi: 10.1152/ajpheart.00061.2004
77.    Kaipio K, Vahlberg T, Suominen M, Pesonen U. The role of non-synonymous NPY gene polymorphism in the nitric oxide production in HUVECs. Biochem Biophys Res Commun. 2009; 381: 587–91.
78.    Olver T, Hiemstra J, Edwards J, et al. Loss of female sex hormones exacerbates cerebrovascular and cognitive dysfunction in aortic banded miniswine through a neuropeptide Y-Ca-activated potassium channel-nitric oxide mediated mechanism. J Am Heart Assoc. 2017; 6:e007409. doi: 10.1161/jaha.117.007409
79.    Sajib S, Zahra F, Lionakis M, et al. Mechanisms of angiogenesis in microbe-regulated inflammatory and neoplastic conditions. Angiogenesis. 2018; 21: 1–4. doi: 10.1007/s10456-017-9583-4
80.    Geetha P, Raksha VR, Ishak MJ, Shanmugasundaram P. A Review on Generalized Anxiety Disorder. Res. J. Pharm. Technol. 2017; 10(11): 4043-4046.
81.    Saraf R, Mahmood F, Amir R, Matyal R. Neuropeptide Y is an angiogenic factor in cardiovascular regeneration. Europ J. Pharm. 2016; 776: 64–70. doi: 10.1016/j.ejphar.2016.02.033
82.    Chen X, Zhou Y, Liang S, et al. Overexpression of UHRF1 promoted the proliferation of vascular smooth cells via the regulation of Geminin protein levels. Biosci Rep. 2019; 39: BSR20181341.
83.    Heeschen C, Weis M, Cooke J. Nicotine promotes arteriogenesis. J Am Coll Cardiol. 2003; 41: 489–96. doi: 10.1016/s0735-1097(02)02818-8
84.    Jiang Z, Zhou Y, Chen X, et al. Different effects of neuropeptide Y on proliferation of vascular smooth muscle cells via regulation of Geminin. Mol Cell Biochem. 2017; 433: 205–11.
85.    Lee E, Michalkiewicz M, Kitlinska J, et al. Neuropeptide Y induces ischemic angiogenesis and restores function of ischemic skeletal muscles. J Clin Invest. 2003; 111: 1853–62. doi: 10.1172/jci16929
86.    Li L, Najafi A, Kitlinska J, et al. Of mice and men: neuropeptide Y and its receptors are associated with atherosclerotic lesion burden and vulnerability. J Cardiovasc Transl Res. 2011; 4: 351–62. doi: 10.1007/s12265-011-9271-5.

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