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Multiple C a 2+ Channel‐Dependent Components in Growth Hormone Secretion from Rat Anterior Pituitary Somatotrophs
Author(s) -
Sosial E.,
Nussinovitch I.
Publication year - 2015
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12240
Subject(s) - secretion , medicine , endocrinology , anterior pituitary , somatotropic cell , basal (medicine) , channel blocker , pituitary gland , biology , chemistry , hormone , calcium , insulin
The involvement of L‐type C a 2+ channels in both ‘basal’ and ‘stimulated’ growth hormone ( GH ) secretion is well established; however, knowledge regarding the involvement of non‐ L ‐type C a 2+ channels is lacking. We investigated whether non‐ L ‐type C a 2+ channels regulate GH secretion from anterior pituitary ( AP ) cells. To this end, GH secretion was monitored from dissociated AP cells, which were incubated for 15 min with 2 m m K + (‘basal’ secretion) or 60 m m K + (‘stimulated’ secretion). The role of non‐L‐type Ca 2+ influx was investigated using specific channel blockers, including ω‐agatoxin‐ IVA , ω‐conotoxin GVIA or SNX ‐482, to block P/Q‐, N‐ or R‐type Ca 2+ channels, respectively. Our results demonstrate that P/Q‐, N‐ and R‐type Ca 2+ channels contributed 21.2 ± 1.9%, 20.2 ± 7.6% and 11.4 ± 1.8%, respectively, to ‘basal’ GH secretion and 18.3 ± 1.0%, 24.4 ± 5.4% and 14.2 ± 4.8%, respectively, to ‘stimulated’ GH secretion. After treatment with a ‘cocktail’ that comprised the previously described non‐L‐type blockers, non‐L‐type Ca 2+ channels contributed 50.9 ± 0.4% and 45.5 ± 2.0% to ‘basal’ and ‘stimulated’ GH secretion, respectively. Similarly, based on the effects of nifedipine (10 μM), L‐type Ca 2+ channels contributed 34.2 ± 3.7% and 54.7 ± 4.1% to ‘basal’ and ‘stimulated’ GH secretion, respectively. Interestingly, the relative contributions of L‐type/non‐L‐type Ca 2+ channels to ‘stimulated’ GH secretion were well correlated with the relative contributions of L‐type/non‐L‐type Ca 2+ channels to voltage‐gated Ca 2+ influx in AP cells. Finally, we demonstrated that compartmentalisation of Ca 2+ channels is important for GH secretion. Lipid raft disruption (methyl‐β‐cyclodextrin, 10 m m ) abrogated the compartmentalisation of Ca 2+ channels and substantially reduced ‘basal’ and ‘stimulated’ GH secretion by 43.2 ± 3.4% and 58.4 ± 4.0%, respectively. In summary, we have demonstrated that multiple Ca 2+ channel‐dependent pathways regulate GH secretion. The proper function of these pathways depends on their compartmentalisation within AP cell membranes.