Adrenoceptors mediating relaxation to catecholamines in rat isolated jejunum

MacDonald, Allan; Forbes, IJ; Gallacher, D V; Heeps, G.; McLaughlin, Daniel P.

doi:10.1111/j.1476-5381.1994.tb13113.x

“…The relative high potency of ß 3 -adrenoceptor agonists was observed, the rank order of potency was BRL37344 1 isoprenaline 1 CGP12177A 1 noradrenaline 1 adrenaline. The order of potency of catecholamines is in agreement with the order in the tissues where ß 3 -adrenoceptor responses have been observed [12]. Since isoprenaline was more potent than noradrenaline and adrenaline, therefore, ß-adrenoceptors were clearly involved in mediating all the agonist responses studied.…”

Section: Discussionsupporting

confidence: 70%

Pharmacological Analysis of Atypical β-Adrenoceptors in the Guinea Pig Gastric Fundus Using the β<sub>3</sub>-Adrenoceptor Antagonist Bupranolol

Horinouchi

¹

,

Koike²

1999

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Atypical β-adrenoceptor-mediated relaxations to catecholamines (isoprenaline, noradrenaline and adrenaline) and β₃-adrenoceptor agonists, BRL37344 [(R*,R*)-(±)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]-propyl]phenoxyacetic acid sodium salt] and CGP12177A [(–)-4-(3-t-butylamino-2-hydroxy- propoxy)benzimidazol-2-one] in guinea pig gastric fundus were investigated. The five agonists induced concentration-dependent relaxation of the gastric fundus. In the presence of both atenolol and butoxamine only small rightward shifts of the concentration-response curves to these agonists were observed. Under this condition, however, bupranolol caused a concentration-dependent rightward shift of the concentration-response curve to catecholamines and β₃-adrenoceptor agonists. Schild plot analyses of bupranolol against these agonists gave pA₂ values of 6.08 (isoprenaline), 6.04 (noradrenaline), 5.90 (adrenaline), 6.50 (BRL37344) and 5.80 (CGP12177A), respectively. These results clearly suggest that the existence of functional atypical β-adrenoceptors in the guinea pig gastric fundus and the relaxation of these agonists in this tissue are mediated via atypical β-adrenoceptors.

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“…They noted that lesion formation correlated with an increase in gastric smooth muscle contraction and motility; both lesion formation and muscular contraction were prevented by the spasmolytic muscarinic antagonist, atropine. Whether muscular contraction and motility are factors in the pathogenesis of NSAID injury to the small intestine has yet to be determined, but β 3 adrenoceptor agonists, known to have spasmolytic activity in the rat small intestine,25 and atropine, are both inhibitors of indomethacin induced jejunal ulceration in the rat 2225 26 …”

Section: Discussionmentioning

confidence: 99%

Vascular anatomy defines sites of indomethacin induced jejunal ulceration along the mesenteric margin

Anthony

¹

,

Pounder

²

,

Dhillon

³

et al. 1997

Gut

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Background-Indomethacin induces ulceration in the rat jejunum with sparing of the ileum. The ulcers localise between vasa recta along the mesenteric margin of the bowel, observations that have not been fully explained. Aim-To examine the relationship between the localisation of experimental ulcers and the vascular anatomy of the rat small intestine. Methods-The normal vascular anatomy of the rat jejunum and ileum was studied and compared using arterial carbon ink perfusion. The anatomical localisation of early and advanced lesions induced by indomethacin was examined with particular reference to the vasculature. Mucosal injury induced by feeding vessel ligation for 24 hours or brief ischaemiareperfusion injury was examined. The existence of anatomically sensitive sites to indomethacin was tested in a two dose study. Results-In the rat jejunum, poorly vascularised sites along the mesenteric margin were highly susceptible to indomethacin induced injury, such sites being absent from the ileum. Villous contraction was a feature of both early indomethacin injury and ischaemia-reperfusion injury in the rat jejunum. Twenty four hour ligation of jejunal vasa brevia selectively induced ischaemic injury along the mesenteric margin. Two doses of indomethacin to rats did not induce greater injury than a single dose. Conclusions-Results support the hypothesis that the rat jejunum possesses vascularly compromised sites along the mesenteric margin that are susceptible to indomethacin induced injury. Indomethacin may cause ischaemia-reperfusion injury selectively at these sites.

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“…They noted that lesion formation correlated with an increase in gastric smooth muscle contraction and motility; both lesion formation and muscular contraction were prevented by the spasmolytic muscarinic antagonist, atropine. Whether muscular contraction and motility are factors in the pathogenesis of NSAID injury to the small intestine has yet to be determined, but 3 adrenoceptor agonists, known to have spasmolytic activity in the rat small intestine, 25 and atropine, are both inhibitors of indomethacin induced jejunal ulceration in the rat. 22 25 26 The predilection of the mesenteric margin to form lesions specifically at a site supplied by smaller feeding vessels raises the possibility that the latter might be more susceptible than the larger vessels to muscular compression.…”

Section: Discussionmentioning

confidence: 99%

Vascular anatomy defines sites of indomethacin induced jejunal ulceration along the mesenteric margin

Anthony¹,

Pounder²,

Dhillon³

et al. 1998

European Journal of Gastroenterology & Hepatology

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Background-Indomethacin induces ulceration in the rat jejunum with sparing of the ileum. The ulcers localise between vasa recta along the mesenteric margin of the bowel, observations that have not been fully explained. Aim-To examine the relationship between the localisation of experimental ulcers and the vascular anatomy of the rat small intestine. Methods-The normal vascular anatomy of the rat jejunum and ileum was studied and compared using arterial carbon ink perfusion. The anatomical localisation of early and advanced lesions induced by indomethacin was examined with particular reference to the vasculature. Mucosal injury induced by feeding vessel ligation for 24 hours or brief ischaemiareperfusion injury was examined. The existence of anatomically sensitive sites to indomethacin was tested in a two dose study. Results-In the rat jejunum, poorly vascularised sites along the mesenteric margin were highly susceptible to indomethacin induced injury, such sites being absent from the ileum. Villous contraction was a feature of both early indomethacin injury and ischaemia-reperfusion injury in the rat jejunum. Twenty four hour ligation of jejunal vasa brevia selectively induced ischaemic injury along the mesenteric margin. Two doses of indomethacin to rats did not induce greater injury than a single dose. Conclusions-Results support the hypothesis that the rat jejunum possesses vascularly compromised sites along the mesenteric margin that are susceptible to indomethacin induced injury. Indomethacin may cause ischaemia-reperfusion injury selectively at these sites.

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Adrenoceptors mediating relaxation to catecholamines in rat isolated jejunum

Cited by 22 publications

References 13 publications

Pharmacological Analysis of Atypical β-Adrenoceptors in the Guinea Pig Gastric Fundus Using the β<sub>3</sub>-Adrenoceptor Antagonist Bupranolol

Pharmacological Analysis of Atypical β-Adrenoceptors in the Guinea Pig Gastric Fundus Using the β<sub>3</sub>-Adrenoceptor Antagonist Bupranolol

Vascular anatomy defines sites of indomethacin induced jejunal ulceration along the mesenteric margin

Vascular anatomy defines sites of indomethacin induced jejunal ulceration along the mesenteric margin

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