Distribution and Types of Adrenoceptors in the Guinea‐pig Ileum: The Action of Α‐ and Β‐adrenoceptor Agonists

Abstract

1 Segments of guinea-pig ileum and the myenteric plexus-longitudinal smooth muscle preparation were used for a study of the actions of adrenaline, noradrenaline, isoprenaline, ephedrine and phenylephrine on the responses of coaxially stimulated ileum at different distances from the ileocaecal valve. 2 The responses of the ileum to electrical stimulation were suppressed by adrenaline, noradrenaline and ephedrine, while phenylephrine and isoprenaline inhibited them only partially. 3 The twitch inhibition elicited by these adrenoceptor agonists was the same at all distances from the ileocaecal valve. There was no significant difference between their cumulative and non-cumulative concentration-response curves. 4 Smooth muscle relaxation was induced only by isoprenaline and contraction only by phenylephrine at all distances from the ileocaecal junction. Adrenaline and noradrenaline evoked smooth muscle contraction in the terminal (0 to 20 cm), a concentration-dependent, biphasic response in the intermediate part (21 to 50 cm) and a relaxation in the proximal ileum (>50 cm from the ilecocaecal valve). Ephedrine did not change significantly the smooth muscle tension in the terminal and the intermediate segments and induced smooth muscle relaxation in the proximal ones. 5 Ouabain and a potassium-free solution did not appear to influence the prejunctional action of noradrenaline nor the amplitude of smooth muscle relaxation in the proximal ileum, whereas the concentration-contractor response curves were significantly depressed and shifted to the right by ouabain and in a potassium-free solution. 6 The brief initial (phasic) contraction induced by acetylcholine was not influenced during the sustained increase or decrease in tension induced by catecholamines. On the contrary, the stimulatory catecholamine actions disappeared or were changed to smooth muscle relaxation by acetylcholine pretreatment. Potassium chloride pretreatment did not change the character of the adrenoceptor agonist action of the agonists studied. 7 Since there is a similar prejunctional action at all distances from the ileocaecal valve and a different postjunctional effect of the adrenoceptor agonists at different distances from the ileocaecal junction, it could be suggested that in the guinea-pig ileum there are at least two x-adrenoceptors (inhibitory prejunctional-22, stimulatory postjunctional-ol), an inhibitory postjunctional f,-adrenoceptor and an as yet uncharacterized inhibitory postjunctional receptor. 8 Based on the specific postjunctional action of phenylephrine and the prejunctional action of ephedrine in the guinea-pig ileum, these drugs could be used with success as 'specific' z1-and x2-adrenoceptor stimulants.

Distribution and Types of Adrenoceptors in the Guinea‐pig Ileum: The Action of Α‐ and Β‐adrenoceptor Blocking Agents

“…The twitch inhibition, in agreement with findings of Drew (1978) Hduced by noradrenaline (0.01 to 100 tLM), ephedrine (0.5 to 1000 iM), adrenaline (0.1 to 10011M), isoprenaline (0.01 to 100 jsM) and phenylephrine (0.1 to 1000 p1M) applied cumulatively showed no significant differences in both the terminal and proximal regions of the whole ileum and the longitudinal musclemyenteric plexus preparation (see also Bauer, 1981). Therefore the results were considered together, when the interactions between agonists and antagonists were studied.…”

“…The postjunctional excitatory al-and inhibitory P-adrenoceptors could be detected not only in the terminal but also in the proximal parts of the ileum (Bauer, 1981), in agreement with the findings of Anderson & Lees (1976) and Wikberg (1978). It has been suggested that a pharmacological difference exists between inhibitory prejunctional and excitatory postjunctional adrenoceptors, as in other smooth muscle preparations (Langer, 1974;Starke, Endo & Taube, 1975;Drew, 1977a) and that an inhibitory postjunctional aadrenoceptor, which is as yet uncharacterized, is also present (Bauer, 1981).…”

“…However, in the present and other experiments the results indicate that the adrenoceptor agonists were stimulating the muscle via x-adrenoceptors and not 5-hydroxytryptamine receptors. While the excitatory postjunctional receptors present in the ileal smooth muscle are of the al-adrenoceptor type (Bauer, 1981), the inhibitory postjunctional ones seem closer to the a2-adrenoceptor subtype, being predominantly stimulated by ephedrine and noradrenaline and inhibited by yohimbine.…”

α2‐Adrenoceptor‐mediated contractile response to catecholamines in smooth muscle strips isolated from rainbow trout stomach (Salmo gairdneri)

“…They are aol-, a2-and P-adrenoceptors: aland P-adrenoceptors are present on the smooth muscle cells. Activation of P-adrenoceptors causes relaxation and that of a,-adrenoceptors causes relaxation or contraction of the intestinal smooth muscle (Bowman & Hall, 1970;Wikberg, 1977;Bauer, 1981;Sahyoun et al, 1982). On the other hand, x2-adrenoceptors are present on both enteric cholinergic nerve terminals and smooth muscle cells.…”

“…On the other hand, x2-adrenoceptors are present on both enteric cholinergic nerve terminals and smooth muscle cells. X2-Adrenoceptors on the prejunctional site regulate cholinergic neurotransmission in an inhibitory manner (Gillespie & Khoyi, 1977;Wikberg, 1977;Drew, 1978;Bauer, 1981;Nakahata et al, 1982) and those on smooth muscle cells (postjunctional site) participate in smooth muscle contraction (Sahyoun et al, 1982) or smooth muscle relaxation (Bauer, 1982;Bauer & Kuriyama, 1982).…”