Stimulatory effect of β-adrenergic agonists on ileal L cell secretion and modulation by α-adrenergic activation

Postprandial release of peptide YY (PYY) and glucagonlike peptide-1 (GLP-1) from L cells results from both nutrient transit in the ileal lumen and neural drive of endocrine cells. The adrenosympathetic system and its effecters have been shown to induce secretion of L cells in vivo or in vitro. Because these transmitters act through three receptors, beta, alpha 1, alpha 2, coupled to different intracellular pathways, we evaluated the responses oft cells to specific agonists, using the model of isolated vascularly perfused rat ileum. General stimulation of adrenergic receptors with epinephrine (10(-7) M) induced significant GLP-1 and PYY secretions (94 +/- 38 and 257 +/- 59 fmol/8 min respectively) which were abolished upon propranolol (10(-7) M) pretreatment and strongly decreased upon infusion with 10(-8) M prazosin. Blockade of alpha 2-receptors with idazoxan (10(-8) M) did not alter epinephrine-induced peptide secretion. The beta-adrenergic agonist isoproterenol (10(-6) M) infused for 30 min induced a transient release of GLP-1 and PW (integrated release over the 8 min of the peak secretion: 38 +/- 16 and 214 +/- 69 fmol for GLP-1 and PYY respectively, P<0.05). Because terbutaline but not dobutamine or BRL 37,344 (10(-5) M) induced significant GLP-1 and PYY secretions (135 +/- 30 and 305 +/- 39 fmol/8 min respectively), isoproterenol-induced secretions are suggested to result mainly from stimulation of the beta 2-isoreceptor type. In contrast, the alpha 1-agonist phenylephrine (10(-7) M) did not stimulate peptide release. When co-infused with 10(-6) M or 10(-7) M isoproterenol, 10(-7) M phenylephrine raised GLP-1 release to 174 +/- 53 and 108 +/- 28 fmol/8 min respectively (vs 38 +/- 16 and 35 +/- 10 fmol/8 min for isoproterenol alone, P<0.05) whereas PYY secretion was not significantly increased. Clonidine (10(-7) M), an alpha 2-agonist, induced a moderate and delayed increase of GLP-1 and PYY but abolished the isoproterenol-induced peptide secretion. Our results showed that general stimulation of adrenergic receptors stimulates the secretory activity of ileal endocrine L cells. The net peptide secretion results from the activation of the beta 2-isoreceptor type. Additionally, GLP-1 and PYY secretions are positively modulated by alpha 1-receptor stimulation and inhibited by alpha 2-receptor activation upon beta-receptor occupation.