Jejunal-ileal differences in dopaminergic but not alpha-adrenergic antisecretory effects

Abstract

Clonidine, an alpha-adrenergic agonist, and apomorphine, a dopaminergic agonist, inhibit water secretion in rat intestine induced by dibutyryl cAMP (DBcAMP) in situ. Apomorphine reversed DBcAMP-induced secretion in ileum and jejunum with ED50 values of 90 and 200 nM, respectively. ED50 values for clonidine's antisecretory effect were 32 and 2 microM in ileum and jejunum, respectively. The antisecretory effects of both clonidine and apomorphine were blocked by the alpha-adrenergic antagonist phentolamine and by the dopaminergic antagonists halo-peridol and sulpiride. Phentolamine was about 10-fold more potent against clonidine than against apomorphine in the ileum and the jejunum. Haloperidol and sulpiride were at least 10-fold more potent against apomorphine than against clonidine in the ileum. In contrast, in the jejunum, haloperidol was equally potent in blocking effects of both agonists, while sulpiride did not block the apomorphine effect. The data are consistent with the presence of both alpha 2-adrenergic and DA2-dopaminergic receptors that stimulate absorption in the ileum. In the jejunum, antisecretory effect appears to be mediated by an action on either an alpha 2-adrenergic or a dopaminergic receptor with characteristics different from those of peripheral DA1- or DA2-receptors.