Investigation of the mechanism of nicotine-induced relaxation in guinea pig gallbladder.
BACKGROUND
Muscular contraction of the gallbladder is the primary determinant of bile delivery into duedonum. Gallbladder filling and emptying are influenced by both inhibitory and excitatory stimuli, and NO plays a key role in normal relaxation. In this study, to determine whether nicotine acts on the gallbladder muscle, the mechanism of its effect on strips of guinea pig gallbladder was studied in vitro.


METHODS
Guinea pig gallbladder muscle strips were mounted in organ bath with modified Krebs-Henseleit solution and aerated with Carbogen. Tension was measured with isometric force transducers, and muscle relaxation was expressed as percent decrease of precontraction induced by carbachol.


RESULTS
Nicotine produced concentration dependent relaxation when preparations were precontracted by carbachol (10(-6) M). Nicotine-induced relaxation was 51.6 +/- 3.2% of phenylephrine contraction and was not affected by guanethidine (10(-5) M), propranolol (10(-6) M), hexamethonium (10(-4) M), indomethacin (10(-5) M), N(w)-nitro L-arginine methyl ester (L-NAME) (3 x 10(-5) M), methylene blue (10(-5) M), glibenclamide (10(-5) M), clotrimazole (10(-6) M), tetraethylammonium (3 x 10(-4) M), or 4-aminopyridine (10(-3) M). Nicotine did not exhibit a calcium antagonizing effect.


CONCLUSIONS
From these results, we concluded that nicotine-induced relaxation of the guinea pig gallbladder is not mediated by the release of noradrenaline, nitric oxide (NO), prostaglandins, or a related substance, or by the activation of potassium channels, or by the stimulation of nicotinic cholinoceptors. Further work is needed to determine the cellular mechanism(s) of action by which nicotine acts on gallbladder smooth muscle.
Utkan
N Zafer
NZ
Department of General Surgery, Kocaeli University School of Medicine, Kocaeli, Turkey. nzutkan@hotmail.com <nzutkan@hotmail.com>
Utkan
Tijen
T
Sarioglu
Yusuf
Y
Cantürk
N Zafer
NZ
Okay
Erdem
E
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005704:Gallbladder / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D009994:Osmolar Concentration; D010656:Phenylephrine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D018679:Cholinergic Agonists; D018722:Nicotinic Agonists; D010656:Phenylephrine; D009538:Nicotine; D002217:Carbachol