CNS Site of Action and Brainstem Circuitry Responsible for the Intravenous Effects of Nicotine on Gastric Tone

Overview

Journal J Neurosci

Specialty Neurology

Date 2002 Mar 30

PMID 11923442

Citations 21

Authors

Manuel Ferreira Jr

Niaz Sahibzada

Min Shi

William Panico

Mark Niedringhaus

Adam Wasserman

Kenneth J Kellar

Joseph Verbalis

Richard A Gillis

Affiliations

Soon will be listed here.

Abstract

The purposes of our study were to determine (1) the effects of intravenous (i.v.) nicotine on gastric mechanical function of anesthetized rats, (2) the CNS site of action of nicotine to produce these effects, (3) the CNS nicotinic acetylcholine receptor (nAChR) subtype(s) responsible for mediating the i.v. effects of nicotine, and (4) the brainstem neurocircuitry engaged by i.v. nicotine for eliciting its gastric effects. This was accomplished by monitoring intragastric pressure (gastric tone) and contractility of the fundus and antrum while administering five doses of i.v. nicotine and microinjecting nicotine into specific brainstem nuclei. Additionally, c-Fos expression in the brainstem after i.v. nicotine and pharmacological agents were used as tools to identify the CNS site and circuitry and reveal the nAChR subtype(s) mediating the gastric effects of nicotine. Using these experimental approaches, we found the following. (1) When given intravenously in doses of 56.5, 113, 226, 452, and 904 nmol/kg, nicotine elicited only inhibitory effects on gastric mechanical function. The most sensitive area of the stomach to nicotine was the fundus, and this effect was mediated by the vagus nerve at doses of 56.5, 113, and 226 nmol/kg. (2) The CNS site of action and nAChR subtype responsible were glutamatergic vagal afferent nerve terminals in the medial subnucleus of the tractus solitarious (mNTS) and alpha4beta2, respectively. (3) The brainstem neurocircuitry that was involved appeared to consist of a mNTS noradrenergic pathway projecting to the dorsal motor nucleus of the vagus (DMV). This pathway seems to be activated via nitriergic interneurons engaged by vagally released glutamate in the mNTS and results in alpha2 adrenergic receptor-mediated inhibition of DMV neurons projecting to the fundus and controlling gastric tone.

Citing Articles

CNS sites controlling the gastric pyloric sphincter: Neuroanatomical and functional study in the rat.

Richardson J, Dezfuli G, Mangel A, Gillis R, Vicini S, Sahibzada N J Comp Neurol. 2023; 531(15):1562-1581.

PMID: 37507853 PMC: 10430764. DOI: 10.1002/cne.25530.

Availability of Central α4β2* Nicotinic Acetylcholine Receptors in Human Obesity.

Schweickert de Palma E, Gunnewig T, Rullmann M, Luthardt J, Hankir M, Meyer P Brain Sci. 2022; 12(12).

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Brainstem activation of GABA receptors in the nucleus tractus solitarius increases gastric motility.

Bellusci L, Kim E, Garcia DuBar S, Gillis R, Vicini S, Sahibzada N Front Neurosci. 2022; 16:961042.

PMID: 35983226 PMC: 9379309. DOI: 10.3389/fnins.2022.961042.

Interactions between Brainstem Neurons That Regulate the Motility to the Stomach.

Bellusci L, Garcia DuBar S, Kuah M, Castellano D, Muralidaran V, Jones E J Neurosci. 2022; 42(26):5212-5228.

PMID: 35610046 PMC: 9236295. DOI: 10.1523/JNEUROSCI.0419-22.2022.

Brainstem Neuronal Circuitries Controlling Gastric Tonic and Phasic Contractions: A Review.

Gillis R, Dezfuli G, Bellusci L, Vicini S, Sahibzada N Cell Mol Neurobiol. 2021; 42(2):333-360.

PMID: 33813668 PMC: 9595174. DOI: 10.1007/s10571-021-01084-5.

References

Krowicki Z, Sivarao D, Abrahams T, Hornby P . Excitation of dorsal motor vagal neurons evokes non-nicotinic receptor-mediated gastric relaxation. J Auton Nerv Syst. 1999; 77(2-3):83-9. View

Doxey J, Lane A, Roach A, Virdee N . Comparison of the alpha-adrenoceptor antagonist profiles of idazoxan (RX 781094), yohimbine, rauwolscine and corynanthine. Naunyn Schmiedebergs Arch Pharmacol. 1984; 325(2):136-44. DOI: 10.1007/BF00506193. View

Sesoko S, Muratani H, Yamazato M, Teruya H, Takishita S, Fukiyama K . Contribution of alpha 2-adrenoceptors in caudal ventrolateral medulla to cardiovascular regulation in rat. Am J Physiol. 1998; 274(4):R1119-24. DOI: 10.1152/ajpregu.1998.274.4.R1119. View

Panico W, Cavuto N, Kallimanis G, Nguyen C, Armstrong D, Benjamin S . Functional evidence for the presence of nitric oxide synthase in the dorsal motor nucleus of the vagus. Gastroenterology. 1995; 109(5):1484-91. DOI: 10.1016/0016-5085(95)90634-7. View

Luetje C, Patrick J . Both alpha- and beta-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors. J Neurosci. 1991; 11(3):837-45. PMC: 6575344. View

Nowak A, Jonderko K, Kaczor R, Nowak S, Skrzypek D . Cigarette smoking delays gastric emptying of a radiolabelled solid food in healthy smokers. Scand J Gastroenterol. 1987; 22(1):54-8. DOI: 10.3109/00365528708991856. View

Jackson H, Nemeth E, Parks T . Non-N-methyl-D-aspartate receptors mediating synaptic transmission in the avian cochlear nucleus: effects of kynurenic acid, dipicolinic acid and streptomycin. Neuroscience. 1985; 16(1):171-9. DOI: 10.1016/0306-4522(85)90054-5. View

GOMEZ R, Ernsberger P, Feinland G, Reis D . Rilmenidine lowers arterial pressure via imidazole receptors in brainstem C1 area. Eur J Pharmacol. 1991; 195(2):181-91. DOI: 10.1016/0014-2999(91)90534-w. View

Ferreira M, Ebert S, Perry D, Yasuda R, Baker C, Davila-Garcia M . Evidence of a functional alpha7-neuronal nicotinic receptor subtype located on motoneurons of the dorsal motor nucleus of the vagus. J Pharmacol Exp Ther. 2001; 296(2):260-9. View

10.

Rinaman L, Verbalis J, Stricker E, Hoffman G . Distribution and neurochemical phenotypes of caudal medullary neurons activated to express cFos following peripheral administration of cholecystokinin. J Comp Neurol. 1993; 338(4):475-90. DOI: 10.1002/cne.903380402. View

11.

Talman W, Andreasen K, Calvin J . Cholecystokinin in nucleus tractus solitarii modulates tonic and phasic gastric pressure. Am J Physiol. 1991; 261(1 Pt 2):R217-22. DOI: 10.1152/ajpregu.1991.261.1.R217. View

12.

Krowicki Z, Sharkey K, Serron S, Nathan N, Hornby P . Distribution of nitric oxide synthase in rat dorsal vagal complex and effects of microinjection of nitric oxide compounds upon gastric motor function. J Comp Neurol. 1997; 377(1):49-69. DOI: 10.1002/(sici)1096-9861(19970106)377:1<49::aid-cne6>3.0.co;2-j. View

13.

Swanson L, SIMMONS D, Whiting P, Lindstrom J . Immunohistochemical localization of neuronal nicotinic receptors in the rodent central nervous system. J Neurosci. 1987; 7(10):3334-42. PMC: 6569159. View

14.

McGehee D, Role L . Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons. Annu Rev Physiol. 1995; 57:521-46. DOI: 10.1146/annurev.ph.57.030195.002513. View

15.

Ferreira M, Singh A, Dretchen K, Kellar K, GILLIS R . Brainstem nicotinic receptor subtypes that influence intragastric and arterial blood pressures. J Pharmacol Exp Ther. 2000; 294(1):230-8. View

16.

Kohagen K, Kim M, McDonnell W, Chey W, Owyang C, Hasler W . Nicotine effects on prostaglandin-dependent gastric slow wave rhythmicity and antral motility in nonsmokers and smokers. Gastroenterology. 1996; 110(1):3-11. DOI: 10.1053/gast.1996.v110.pm8536873. View

17.

Harvey S, Luetje C . Determinants of competitive antagonist sensitivity on neuronal nicotinic receptor beta subunits. J Neurosci. 1996; 16(12):3798-806. PMC: 6578601. View

18.

Talman W, Perrone M, Reis D . Evidence for L-glutamate as the neurotransmitter of baroreceptor afferent nerve fibers. Science. 1980; 209(4458):813-5. DOI: 10.1126/science.6105709. View

19.

Hieble J, DeMarinis R, Fowler P, Matthews W . Selective alpha-2 adrenoceptor blockade by SK&F 86466: in vitro characterization of receptor selectivity. J Pharmacol Exp Ther. 1986; 236(1):90-6. View

20.

Fukuda A, Minami T, Nabekura J, Oomura Y . The effects of noradrenaline on neurones in the rat dorsal motor nucleus of the vagus, in vitro. J Physiol. 1987; 393:213-31. PMC: 1192390. DOI: 10.1113/jphysiol.1987.sp016820. View