title: Characterisation of pre- and post-synaptic alpha-adrenoceptors in modulation of the rat ileum longitudinal and circular muscle activities.
abstract: Previous study has shown that alpha2D-adrenoceptors are involved in modulation of peristalsis in the rat ileum. The aim of the present study was to determine the tissue location of alpha-adrenoceptors in the rat ileum by using a recently devised method. The pre-synaptic alpha-adrenoceptors were characterised by measuring the potencies of agonists to inhibit transmurally-evoked (1 ms pulses, 10 Hz, 8-10 s trains) contractions of the longitudinal and circular muscles and the affinities of antagonists. Post synaptic alpha-adrenoceptors were identified by screening agonists and antagonists in carbachol-contracted tissues. In the circular muscle the order of potencies for inhibiting transmurally-induced contraction was: clonidine > or = oxymetazoline > or = UK 14,304 > or = guanfacine > talipexole > phenylephrine > azepexole. The potency ratios relative to clonidine correlated to those previously derived using the rat ileum peristaltic reflex preparation. Most of the alpha-adrenoceptor agonists, however, caused only small inhibitions of the longitudinal muscle contraction in response to transmural stimulation, except phenylephrine and azepexole. RX 821002, yohimbine, rauwolscine, BRL 44408, phentolamine, idazoxan, ARC 239, and prazosin inhibited the effect of clonidine on the circular muscle response with apparent pK(B) values best correlated with pK(B) or pKi values derived from the rat ileum peristaltic reflex preparation and other tissues known to have the alpha2D-subtype. The rank order of potencies at inhibiting carbachol-induced responses of both muscle layers was: phenylephrine > or = oxymetazoline > clonidine > or = talipexole > azepexole >> guanfacine. UK 14,304 was inactive up to 10 microM. The EC50 value of each agonist on the longitudinal muscle was not significantly different to the corresponding value on the circular muscle. Prazosin was more potent than yohimbine at inhibiting the relaxant effect of phenylephrine in both muscle layers of carbachol-contracted tissues. It is concluded that the recently identified alpha2D-adrenoceptors of the rat ileum are located on cholinergic neurons controlling circular muscle contraction. The study also demonstrated the presence of postsynaptic alpha1-adrenoceptors involved in mediating relaxation in both muscle layers.
authors.affiliation: Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, Parkville, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: I M
authors.initials: IM
authors.lastname: Coupar
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D009119:Muscle Contraction; D010109:Oxymetazoline; D010646:Phentolamine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D017661:Receptors, Presynaptic; D000068438:Brimonidine Tartrate; D010109:Oxymetazoline; C058525:2-methoxyidazoxan; D003000:Clonidine; D019329:Idazoxan; D010646:Phentolamine