Excitatory peptides and osmotic pressure modulate mechanosensitive cation channels in concert.
Behavioral and neuroendocrine responses underlying systemic osmoregulation are synergistically controlled by osmoreceptors and neuropeptides released within the hypothalamus. Although mechanisms underlying osmoreception are understood, the cellular basis for the integration of osmotic and peptidergic signals remains unknown. Here we show that the excitatory effects of angiotensin II, cholecystokinin and neurotensin on supraoptic neurosecretory neurons are due to the stimulation of the stretch-inactivated cation channels responsible for osmoreception. This molecular convergence underlies the facilitatory effects of neuropeptides on responses to osmotic stimulation and provides a basis for the gating effects of plasma osmolality on the responsiveness of osmoregulatory neurons to peptidergic stimulation.
Chakfe
Y
Y
Centre for Research In Neuroscience, Montreal General Hospital and McGill University, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada.
Bourque
C W
CW
D000200:Action Potentials / Q000187:drug effects; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002412:Cations / Q000378:metabolism*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005682:Gadolinium / Q000494:pharmacology; D007032:Hypothalamus, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007038:Hypotonic Solutions / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D009490:Neurosecretory Systems / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism / Q000494:pharmacology; D009997:Osmotic Pressure / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013779:Tetrodotoxin / Q000494:pharmacology
D002412:Cations; D002712:Chlorides; D007038:Hypotonic Solutions; D007473:Ion Channels; D009479:Neuropeptides; D000804:Angiotensin II; D009496:Neurotensin; D013779:Tetrodotoxin; D002766:Cholecystokinin; D005682:Gadolinium; D011188:Potassium