Neuropeptide Y and peptide YY inhibit excitatory synaptic transmission in the rat dorsal motor nucleus of the vagus.
Pancreatic polypeptides (PPs) such as neuropeptide Y (NPY) and peptide YY (PYY) exert profound, vagally mediated effects on gastrointestinal (GI) motility and secretion. Whole-cell patch clamp recordings were made from brainstem slices containing identified GI-projecting rat dorsal motor nucleus of the vagus (DMV) neurons to determine the mechanism of action of PPs. Electrical stimulation of nucleus tractus solitarii (NTS) induced excitatory postsynaptic currents (EPSCs) that were reduced in a concentration-dependent manner by NPY and PYY (both at 0.1-300 nM) in 65 % of the neurons. An increase in the paired-pulse ratio without changes in the postsynaptic membrane input resistance or EPSC rise and decay time suggested that the effects of PPs on EPSCs were due to actions at presynaptic receptors. The Y1 and Y2 receptor selective agonists [Leu31,Pro34]NPY and NPY(3-36) (both at 100 nM) mimicked the inhibition of NPY and PYY on the EPSC amplitude. The effects of 100 nM NPY, but not PYY, were antagonized partially by the Y1 receptor selective antagonist BIBP3226 (0.1 micro M). In addition, the inhibition of the EPSC amplitude induced by NPY, but not PYY, was attenuated partially by pretreatment with the alpha2 adrenoceptor antagonist yohimbine (10 micro M), and occluded partially by the alpha2 adrenoceptor agonist UK14,304 (10 micro M) as well as by pretreatment with reserpine. Pretreatment with a combination of BIBP3226 and yohimbine almost completely antagonized the NPY-mediated effects on EPSCs. Contrary to the inhibition of EPSCs, perfusion with PPs had no effect on the amplitude of inhibitory postsynaptic currents (IPSCs) and a minimal effect on a minority of DMV neurons. Differences in the receptor subtypes utilized and in the mechanism of action of NPY and PYY may indicate functional differences in their roles within the circuitry of the dorsal vagal complex (DVC).
Departments of Internal Medicine - Gastroenterology and Physiology, University of Michigan, Ann Arbor, MI 48109-0682, USA.
Kirsteen N
KN
Browning
R Alberto
RA
Travagli
D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D019894:Peptide YY / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000317:Adrenergic alpha-Antagonists; C092926:BIBP 3226; D009478:Neuropeptide Y; D019894:Peptide YY; D015016:Yohimbine; D012110:Reserpine; D001120:Arginine