Alteration in contractile G-protein coupled receptor expression by moist snus and nicotine in rat cerebral arteries

Journal Article · Fri Apr 15 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.01.016· OSTI ID:21535275

Sandhu, Hardip ^[1]; Cangbao, Xu; Edvinsson, Lars ^[1]

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1. Department of Clinical Experimental Research, Glostrup Research Institute, Ndr. Ringvej 69, 2600 Glostrup (Denmark)

The cardiovascular risk for users of use of Swedish snus/American snuff (moist tobacco) has been debated for a long time. The present study was designed to examine the effects of water- or lipid-soluble (DMSO-soluble) snus and nicotine, the most important substance in tobacco, on the expression of vasocontractile G-protein coupled receptors (GPCR), such as endothelin ET{sub B}, serotonin 5-HT{sub 1B}, and thromboxane A{sub 2} TP receptors, in rat cerebral arteries. Studies show that these vasocontractile GPCR show alterations by lipid-soluble cigarette smoke particles via activation of mitogen-activated protein kinases (MAPK). However, the effects of moist tobacco on the expression of GPCR are less studied. Rat middle cerebral arteries were isolated and organ cultured in serum-free medium for 24 h in the presence of water-soluble snus (WSS), DMSO-soluble snus (DSS), or nicotine. The dose of snus and nicotine was kept at plasma level of snus users (25 ng nicotine/ml). A high dose (250 ng nicotine/ml) was also included due to the previous results showing alteration in the GPCR expression by nicotine at this concentration. Contractile responses to the ET{sub B} receptor agonist sarafotoxin 6c, 5-HT{sub 1B} receptor agonist 5-carboxamidotryptamine, and TP receptor agonist U46619 were investigated by a sensitive myograph. The expression of ET{sub B}, 5-HT{sub 1B}, and TP receptors was studied at mRNA and protein levels using quantitative real-time PCR and immunohistochemistry, respectively. Organ culture with WSS or DSS (25 ng nicotine/ml) lowered the 5-HT{sub 1B} receptor-mediated contraction. Furthermore, DSS shifted the TP receptor-mediated contraction curve left-wards with a stronger contraction. High dose of nicotine (250 ng nicotine/ml) increased the ET{sub B} receptor-mediated contraction. The combined 5-HT{sub 1B} and 5-HT{sub 2A} receptor-mediated contraction was increased, and both the 5-CT and TxA2 induced contractions were left-ward shifted by WSS, DSS, or nicotine (250 ng nicotine/ml). Only the DSS group showed that the increase of 5-HT{sub 1B} receptor-mediated contraction occurred at the transcriptional level, demonstrated by an increased mRNA expression for the receptor. Thus, snus and nicotine alter the GPCR expression in the cerebral arteries, which may be involved in cerebral vascular disease.

• OSTI ID: 21535275
• Journal Information: Toxicology and Applied Pharmacology, Vol. 252, Issue 2; Other Information: DOI: 10.1016/j.taap.2011.01.016; PII: S0041-008X(11)00033-0; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CEREBRAL ARTERIES
CONTRACTION
DOSES
GTP-ASES
HAZARDS
LIPIDS
MESSENGER-RNA
NICOTINE
PHOSPHOTRANSFERASES
POLYMERASE CHAIN REACTION
RATS
RECEPTORS
SEROTONIN
TISSUE CULTURES
TOBACCO
TOBACCO SMOKES
VASCULAR DISEASES
ACID ANHYDRASES
AEROSOLS
ALKALOIDS
AMINES
ANIMALS
AROMATICS
ARTERIES
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZINES
AZOLES
BLOOD VESSELS
BODY
CARDIOVASCULAR DISEASES
CARDIOVASCULAR SYSTEM
COLLOIDS
DISEASES
DISPERSIONS
DRUGS
ENZYMES
GENE AMPLIFICATION
HETEROCYCLIC COMPOUNDS
HYDROLASES
HYDROXY COMPOUNDS
INDOLES
MAMMALS
MEMBRANE PROTEINS
NEUROREGULATORS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PARASYMPATHOLYTICS
PARASYMPATHOMIMETICS
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
PYRIDINES
PYRROLES
PYRROLIDINES
RADIOPROTECTIVE SUBSTANCES
RESIDUES
RESPONSE MODIFYING FACTORS
RNA
RODENTS
SMOKES
SOLS
SYMPATHOMIMETICS
TRANSFERASES
TRYPTAMINES
VERTEBRATES