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

Abstract

Postprandial release of peptide YY (PYY) and glucagon-like 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 effectors have been shown to induce secretion of L cells in vivo or in vitro. Because these transmitters act through three receptors, β, α1, α2, coupled to different intracellular pathways, we evaluated the responses of L 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 10-8M prazosin. Blockade of α2-receptors with idazoxan (10-8M) did not alter epinephrine- induced peptide secretion. The β-adrenergic agonist isoproterenol (10-6 M) infused for 30 min induced a transient release of GLP-1 and PYY (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 β2-isoreceptor type. In contrast, the α1-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 α2-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 β2-isoreceptor type. Additionally, GLP-1 and PYY secretions are positively modulated by α1- receptor stimulation and inhibited by α2-receptor activation upon β- receptor occupation.