title: Inhibitory effects of NPY on ganglionic transmission in myenteric neurones of the guinea-pig descending colon.
abstract: Intracellular recordings were made from myenteric neurones of the guinea-pig descending colon. Neuropeptide Y (NPY) and related pancreatic polypeptides were applied by superfusion and the effects upon the amplitude of fast excitatory synaptic potentials (ESPs) and the ratio of paired fast ESPs evoked by stimulation of internodal fibre tracts were noted. NPY produced a concentration-dependent inhibition in fast ESP amplitude in the majority of neurones (17/21) with a calculated IC50 value of 7 nM; in some neurones this inhibition was mediated via the local release of noradrenaline. Peptide YY (PYY) (eight out of 11 neurones; IC50 = 1 nM), NPY(3-36) (three out of three neurones) and [Leu31, Pro34]NPY (four out of five neurones) also decreased the amplitude of fast ESPs. The effects of two or more pancreatic polypeptides or analogues on fast synaptic transmission were compared directly in six neurones; the apparent relative potency of agonists suggested the involvement of Y2-receptors and at least one other Y-receptor type. In the absence of any direct postsynaptic effects of pancreatic polypeptides on the active or passive properties of myenteric neurones, or on their sensitivity to ionophoretically applied acetylcholine, inhibition of fast ganglionic transmission was presumed to be presynaptic in origin. It is concluded that, in addition to their previously described depressant actions on neuro-effector transmission to colonic smooth muscle, pancreatic polypeptides can exert powerful inhibitory effects on myenteric neurones of the descending colon.
authors.affiliation: Department of Biomedical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB9 1AS UK. kbrowni2@hfhs.org
authors.forename: K N
authors.initials: KN
authors.lastname: Browning
authors.forename: G M
authors.initials: GM
authors.lastname: Lees
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D003106:Colon / Q000294:innervation* / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D019329:Idazoxan / Q000494:pharmacology; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009197:Myenteric Plexus / Q000187:drug effects* / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects*; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010191:Pancreatic Polypeptide / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D009478:Neuropeptide Y; D010446:Peptide Fragments; C113547:neuropeptide Y (3-36); C062259:neuropeptide Y, Leu(31)-Pro(34)-; D010191:Pancreatic Polypeptide; D011433:Propranolol; D003000:Clonidine; D009638:Norepinephrine; D019329:Idazoxan