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.
Department of Neuroendocrinology, AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, U.K.
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Kato
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Chapman
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RJ
Bicknell
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