Prolactin-releasing peptide affects gastric motor function in rat by modulating synaptic transmission in the dorsal vagal complex.
Prolactin-releasing peptide (PrRP) is a recently discovered neuropeptide implicated in the central control of feeding behaviour and autonomic homeostasis. PrRP-containing neurones and PrRP receptor mRNA are found in abundance in the caudal portion of the nucleus tractus solitarius (NTS), an area which together with the dorsal motor nucleus of the vagus (DMV) comprises an integrated structure, the dorsal vagal complex (DVC) that processes visceral afferent signals from and provides parasympathetic motor innervation to the gastrointestinal tract. In this study, microinjection experiments were conducted in vivo in combination with whole-cell recording from neurones in rat medullary slices to test the hypothesis that PrRP plays a role in the central control of gastric motor function, acting within the DVC to modulate the activity of preganglionic vagal motor neurones that supply the stomach. Microinjection of PrRP (0.2 pmol (20 nl)(-1)) into the DMV at the level of the area postrema (+0.2 to +0.6 mm from the calamus scriptorius, CS) markedly stimulated gastric contractions and increased intragastric pressure (IGP). Conversely, administration of peptide into the DMV at sites caudal to the obex (0.0 to -0.3 mm from the CS) decreased IGP and reduced phasic contractions. These effects occurred without change in mean arterial pressure and were abolished by ipsilateral vagotomy, indicating mediation via a vagal-dependent mechanism(s). The pattern of gastric motor responses evoked by PrRP mimicked that produced by administration of L-glutamate at the same sites, and both the effects of L-glutamate and PrRP were abolished following local administration of NMDA and non-NMDA-type glutamate receptor antagonists. On the other hand, microinjection of PrRP into the medial or comissural nucleus of the solitary tract (mNTS and comNTS, respectively) resulted in less robust changes in IGP in a smaller percentage of animals, accompanied by marked alterations in arterial pressure. Superfusion of brain slices with PrRP (100-300 nm) produced a small depolarization and increased spontaneous firing in 10 of 30 retrogradely labelled gastric-projecting DMV neurones. The excitatory effects were blocked by administration of TTX (2 mum) or specific glutamate receptor antagonists, indicating that they resulted from interactions of PrRP at a presynaptic site. Congruent with this, PrRP increased the amplitude of excitatory postsynaptic currents (EPSCs, 154 +/- 33%, 12 of 25 neurones) evoked by electrical stimulation in mNTS or comNTS. In addition, administration of PrRP decreased the paired-pulse ratio of EPSCs evoked by two identical stimuli delivered 100 ms apart (from 0.95 +/- 0.08 to 0.71 +/- 0.11, P < 0.05), whereas it did not affect the amplitude of inward currents evoked by exogenous application of L-glutamate to the slice. The frequency, but not amplitude of spontaneous EPSCs and action potential-independent miniature EPSCs was also increased by administration of PrRP, suggesting that the peptide was acting at least in part at receptors on presynaptic nerve terminals to enhance glutamatergic transmission. In recordings obtained from a separate group of slices, we did not observe any direct effects of PrRP on spontaneous discharge or postsynaptic excitability in either mNTS or comNTS neurones (n = 31). These data indicate that PrRP may act within the DVC to regulate gastric motor function by modulating the efficacy of conventional excitatory synaptic inputs from the NTS onto gastric-projecting vagal motor neurones.
GI Division, Department of Internal Medicine, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0622, USA.
Gintautas
G
Grabauskas
Shi-Yi
SY
Zhou
Sudipto
S
Das
Yuanxu
Y
Lu
Chung
C
Owyang
Hylan C
HC
Moises
D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D005071:Evoked Potentials; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid; D007028:Hypothalamic Hormones / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D056690:Prolactin-Releasing Hormone; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000294:innervation; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D007028:Hypothalamic Hormones; D009479:Neuropeptides; C534379:Prlh protein, rat; D056690:Prolactin-Releasing Hormone; D018698:Glutamic Acid