title: Role of the cholinergic system and of apamin-sensitive Ca2+-activated K+ channels on rabbit jejunum spontaneous activity and on the inhibitory effects of adrenoceptor agonists.
abstract: 1. One reason why rabbit jejunum is suitable for studying the mechanisms underlying the actions of the various neurotransmitters and their interactions is its spontaneous motility. The main regulator of spontaneous motility is the cholinergic system. How the cholinergic system regulates the spontaneous activity in the rabbit jejunum and how it affects the inhibitory action of alpha- and beta-adrenoceptor agonists remains unclear. 2. We studied the influence of the cholinergic system and apamin-sensitive Ca2+-activated K+ channels on spontaneous contractions in the rabbit jejunum and on the inhibitory effects of alpha1- and beta-adrenoceptor agonists. 3. In naïve tissues, atropine (ATR, 7.4 x 10(-8) m) and tetrodotoxin (8 x 10(-8) m) almost completely inhibited - to a similar extent - the amplitude of spontaneous activity. Despite the presence of ATR or TDX, tissue contraction gradually recovered to about 50% of the baseline amplitude within 5-10 min. When ATR or TDX, respectively, were added to the TDX- or ATR-treated tissues, the recovered activity decreased weakly but significantly. After washout and a 45-min rest the contraction amplitude returned to baseline values. A further exposure to ATR or TDX reduced the contraction to a level significantly lower than the one obtained after TDX or ATR added 5 min after ATR or TDX, respectively. In preparations prestimulated for 10 min with acetylcholine (ACh), ATR abolished the TDX-resistant recovered spontaneous activity. 4. Adrenaline (ADR, 0.5-5 x 10(-7) m) and phenylephrine (PHE, 1-10 x 10(-7) m) inhibited tissue motility in naïve and in ATR- and in TDX-exposed preparations. But whereas in naïve preparations the alpha1-adrenoceptor antagonists completely antagonized inhibition induced by both drugs, in ATR- and TDX-exposed tissues they did so only partially for ADR. Agonist-induced inhibition had a rapid onset but rapidly faded; pendular movements took significantly longer to recover in ATR- and TDX-treated tissues than in naïve tissues. In tissues exposed for 2 min to ADR (0.5-5 x 10(-7) m) or PHE (1-10 x 10(-7) m), washout or addition of alpha1-adrenoceptor antagonists caused an immediate short-lasting increase in contraction amplitude. 5. Apamin (APAM, 5 x 10(-9) m) caused a rapid and persistent increase in the amplitude of contractions. It also blocked the inhibitory responses to ADR and PHE, and removed washout-induced contractions. The APAM-induced increase in the contraction amplitude correlated with the increase obtained by washing out ADR or PHE. 6. Isoprenaline (at concentrations up to 2.8 x 10(-7) m) produced no inhibitory response in naïve tissues, but it invariably blocked (at a concentration of 0.7 x 10(-7) m) the recovered spontaneous activity (and sometimes depressed muscletone) in tissues exposed to ATR or TDX. Neither propranolol (3.4 x 10(-7) m) nor APAM (5 x 10(-9) m) counteracted these inhibitory effects. 7. These results indicate that spontaneous motility in the rabbit jejunum is predominantly mediated by neuronal release of ACh and by some other unidentified neuronal activity. Released ACh inhibits myogenic activity and strongly antagonizes beta-adrenoceptor-induced APAM-insensitive inhibition but leaves alpha1 agonist-induced APAM-sensitive inhibition unchanged.
mesh_terms: D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000322:Adrenergic Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism*; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate; D007545:Isoproterenol / Q000494:pharmacology; D007583:Jejunum / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D008297:Male; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000502:physiology*; D011817:Rabbits; D013779:Tetrodotoxin / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D000322:Adrenergic Agonists; D000317:Adrenergic alpha-Antagonists; D024681:Potassium Channels, Calcium-Activated; D010656:Phenylephrine; D001030:Apamin; D013779:Tetrodotoxin; D001285:Atropine; D015544:Inositol 1,4,5-Trisphosphate; D007545:Isoproterenol; D000109:Acetylcholine; D004837:Epinephrine