title: Atrial natriuretic peptide modulates synaptic transmission from osmoreceptor afferents to the supraoptic nucleus.
abstract: Atrial natriuretic peptide (ANP) and its receptors are present in hypothalamic nuclei containing the magnocellular neurosecretory cells (MNCs), which release vasopressin and oxytocin. In the rat, intracerebroventricular injections of ANP inhibit the release of both hormones in response to hypertonicity. Although these findings suggest a role for endogenous ANP in the central control of fluid balance, cellular mechanisms underlying the modulatory actions of ANP are unknown. We therefore examined the effects of ANP on the osmoresponsiveness of MNCs impaled in rat hypothalamic explants. Applications of ANP (75-150 nM) over the supraoptic nucleus did not affect depolarizing responses to local hypertonicity, but they reversibly abolished the synaptic excitation of MNCs after hypertonic stimulation of the organum vasculosum laminae terminalis (OVLT). These effects were associated with decreased spontaneous EPSP (sEPSP) amplitude rather than with changes in sEPSP frequency. Accordingly, application of ANP reduced the amplitude of glutamatergic EPSPs evoked by electrical stimulation of the OVLT (IC50 approximately 3 nM). The inhibitory effects of ANP on EPSP amplitude were mimicked by application of 3'-5'-dibutyryl cGMP, consistent with the guanylate cyclase activity of natriuretic peptide receptors. Although depolarizing responses of MNCs to ionotropic glutamate receptor agonists were unaffected by ANP, the peptide reversibly enhanced paired-pulse facilitation of electrically evoked EPSPs. These results indicate that centrally released ANP may inhibit osmotically evoked neurohypophysial hormone release through presynaptic inhibition of glutamate release from osmoreceptor afferents derived from the OVLT.
authors.affiliation: Centre for Research in Neuroscience, Montreal General Hospital Research Institute and McGill University, Québec, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Richard
authors.forename: C W
authors.initials: CW
authors.lastname: Bourque
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology / Q000502:physiology*; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D009490:Neurosecretory Systems / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009995:Osmosis; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate / Q000187:drug effects; D011984:Sensory Receptor Cells / Q000502:physiology*; D013495:Supraoptic Nucleus / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D017470:Receptors, Glutamate; D009320:Atrial Natriuretic Factor