Activation of kappa-opioid receptors inhibits depolarisation-evoked exocytosis but not the rise in intracellular Ca2+ in secretory nerve terminals of the neurohypophysis.
Nerve endings of the magnocellular neurohypophysial neurones possess kappa-opioid receptors. Using a preparation of isolated terminals from the neurohypophysis we studied kappa-opioid effects on secretion of oxytocin and vasopressin and on intracellular Ca2+ concentration ([Ca2+]i) measured fluorimetrically or using digital video imaging with Fura-2. The dihydropyridine Ca(2+)-channel antagonist nicardipine reduced [Ca2+]i responses to K(+)-depolarisation (30-40 mM K+) by 55-75% and inhibited evoked secretion of oxytocin and vasopressin to a similar extent. The selective kappa-receptor agonist D-Pro10 Dynorphin A 1-11 (DPDYN) substantially inhibited K+ evoked secretion of oxytocin by 40-90% and secretion of arginine vasopressin (AVP) by 20-50%. DPDYN caused only a 10% reduction in the average total population [Ca2+]i response to K+ depolarisation. No sub-population of inhibitory responses was observed when samples of individual terminal [Ca2+]i responses were examined with imaging. Although kappa-receptors are coupled to Ca(2+)-channels at neuronal somata our data suggest that alternative effector mechanisms operate in these secretory nerve endings.
Kato
M
M
Department of Neuroendocrinology, AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, U.K.
Chapman
C
C
Bicknell
R J
RJ
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D004399:Dynorphins / Q000031:analogs & derivatives / Q000494:pharmacology; D005089:Exocytosis / Q000502:physiology*; D005470:Fluorometry; D016257:Fura-2; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009411:Nerve Endings / Q000378:metabolism*; D010121:Oxytocin / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010904:Pituitary Gland, Posterior / Q000378:metabolism*; D051381:Rats; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D014741:Video Recording
D015220:Calcium Channels; D010446:Peptide Fragments; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D001127:Arginine Vasopressin; D010121:Oxytocin; D004399:Dynorphins; C044619:dynorphin (1-11), Pro(10)-; D002118:Calcium; D016257:Fura-2