Activation of portal-hepatic osmoreceptors in rats: role of calcium, acetylcholine and cyclic AMP.
Osmoreceptors are sensory organs of paramount importance in water and electrolyte balance, yet the mechanisms for their activation are virtually unknown. Peripheral osmoreceptors have been localised in the hepatic portal vein area of rats. We thus superfused the portal adventitia with 0.2 ml of 4% NaCl before and after various pharmacological pretreatments (0.4 ml of 1 mM solutions) of the portal area, while monitoring the neural activity of the hypothalamo-neurohypophysial system. Portal superfusion with verapamil, to reduce Ca-influx, reversibly inhibited the response to osmotic stimuli by up to 50% (P less than 0.0005). Such inhibition (58%; P less than 0.0005) was also seen with portal superfusion by atropine. Atropine did not affect hypothalamo-neurohypophysial responses to stimulation of portal bradykinin receptors with 0.2 ml 1 muM bradykinin, and portal superfusion with acetylcholine activated the hypothalamo-neurohypophysial system. The results thus support the hypothesis of a cholinergic neurotransmission linking portal osmoreceptive structures and afferent nerve endings. Diamide, which inhibits water efflux in frog skin, also reversibly inhibited responses to osmotic stimuli by 38% (P less than 0.0005). Pretreatments with trifluoperazine, a calmodulin inhibitor, and cordycepin, an adenylate cyclase inhibitor, diminished responses to osmotic stimuli by 30-45% (P less than 0.005), while cAMP and theophilline potentiated them by 38% (P less than 0.0005). Responses to bradykinin superfusion were reduced 20-30% (P less than 0.05) by both cordycepin and cAMP. The results suggest that portal osmoreceptors release acetylcholine to excite afferent nerves when exposed to an osmotic gradient. The mechanism of this release may be mediated by an efflux of water and an increase of intracellular calcium activity and cAMP.
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002628:Chemoreceptor Cells / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D005071:Evoked Potentials; D005260:Female; D008099:Liver / Q000294:innervation*; D008297:Male; D009994:Osmolar Concentration; D011169:Portal Vein / Q000294:innervation*; D051381:Rats; D011919:Rats, Inbred Strains; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000502:physiology; D014882:Water-Electrolyte Balance
D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D000242:Cyclic AMP; D000109:Acetylcholine; D002118:Calcium