title: Blockage of K+ channels reverses the inhibitory action of atriopeptin on secretagogue-stimulated ACTH release by perifused isolated rat anterior pituitary cells.
abstract: The aim of the present study was to investigate how atriopeptin inhibits secretagogue-stimulated ACTH secretion in vitro. Perifused isolated rat anterior pituitary cells were used throughout; the ACTH content of the perifusate was measured by radioimmunoassay. In the presence of a constant (0.05 nmol/l) concentration of 41-residue corticotrophin-releasing factor (CRF), arginine vasopressin (AVP; 0.05-50 nmol/l) stimulated ACTH secretion in a concentration-dependent manner, the combination of 0.05 nmol CRF/l and 0.5 nmol AVP/l (CRF/AVP) stimulated ACTH release to six- to eightfold above baseline. The effect of CRF/AVP was not modified by tetrodotoxin, but was abolished by CoCl2 and reduced to about 70% of the control stimulus by nifedipine. Application of 103-126 residue atriopeptin for 10 min before and 2.5 min during the CRF/AVP stimulus strongly suppressed the evoked release of ACTH, the maximal inhibition was 75-90% at 10 nmol atriopeptin/l. The calcium ionophore ionomycin (200 nmol/l) reversed the effect of atriopeptin while it had no secretagogue activity of its own, and did not enhance the response to CRF/AVP. A variety of blockers of K+ channels, 4-amino pyridine, tetraethylammonium, apamine, quinine, but not tolbutamide, effectively antagonized the inhibitory action of atriopeptin (10 nmol/l). None of these drugs altered ACTH release evoked by CRF/AVP. In concentration-response experiments, the half effective concentration of 4-aminopyridine and tetraethylammonium were around 1 mmol/l and 10 nmol/l for apamine. Finally, tetraethylammonium and apamine also antagonized the inhibition of CRF/AVP-evoked ACTH release by 8-Br-cGMP.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Human Anatomy, University of Oxford.
authors.forename: F A
authors.initials: FA
authors.lastname: Antoni
authors.forename: G
authors.initials: G
authors.lastname: Dayanithi
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003864:Depression, Chemical; D005260:Female; D015759:Ionomycin / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D010446:Peptide Fragments; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D001127:Arginine Vasopressin; C062525:atrial natriuretic factor prohormone (103-126); D015759:Ionomycin; D019789:Tetraethylammonium; D009320:Atrial Natriuretic Factor; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006152:Cyclic GMP