Characterization of functional nicotinic acetylcholine receptors involved in catecholamine release from the isolated rat adrenal gland.
We tried to characterize nicotinic acetylcholine receptors involved in the release of catecholamines from the rat adrenal gland. The isolated adrenal gland was retrogradely perfused via the adrenal vein with Krebs-Ringer solution at a flow rate of 0.5 ml/min. Endogenous catecholamines, adrenaline and noradrenaline, released into the perfusate were electrochemically measured using high-performance liquid chromatography. (-)-Nicotine (3 x 10(-6)-3 x 10(-5) M) evoked the release of catecholamines (adrenaline >> noradrenaline) in a concentration-dependent manner. The (-)-nicotine (10(-5) M)-induced release of catecholamines was effectively attenuated by mecamylamine (10(-7) and 10(-6) M) (a relatively selective antagonist of alpha3beta4 nicotinic receptors), but not influenced by alpha-bungarotoxin (3 x 10(-7) M) (an antagonist of alpha7 nicotinic receptors) and dihydro-beta-erythroidine (10(-5) M) (a relatively selective antagonist of alpha4beta2 nicotinic receptors). (+/-)-Epibatidine (3 x 10(-7) and 10(-6) M) (a non-selective nicotinic receptor agonist), (-)-cytisine (10(-5) and 10(-4) M) (an agonist of beta4 nicotinic receptors) and (+/-)-2-(3-pyridinyl)-1-azabicyclo(2.2.2)octane (RJR-2429) (10(-5) M) (a putative agonist of alpha3beta4 nicotinic receptors) effectively evoked the release of catecholamines (adrenaline >> noradrenaline), while (E)-N-methyl-4-(3-pyridinyl)-3-butene-1-amine (RJR-2403) (up to 10(-4) M) (a selective agonist of alpha4beta2 nicotinic receptors) had no effect. The efficacies of these agonists are as follows: (+/-) epibatidine >> RJR-2429>(-)-cytisine>(-)-nicotine >> RJR-2403. These results suggest that alpha3beta4 nicotinic receptors are involved in the release of catecholamines from the rat adrenal gland.
Yokotani
Kunihiko
K
Department of Pharmacology, Kochi Medical School, Nankoku, Kochi, 783-8505, Japan yakotani@dtn.am400gw.kochi-ms.ac.jp
Okada
Shoshiro
S
Nakamura
Kumiko
K
D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*
D002395:Catecholamines; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D009538:Nicotine; D004837:Epinephrine