MultipleCa²⁺Channel‐Dependent Components in Growth Hormone Secretion from Rat Anterior Pituitary Somatotrophs

Abstract

The involvement of L-type Ca(2+) channels in both 'basal' and 'stimulated' growth hormone (GH) secretion is well established; however, knowledge regarding the involvement of non-L-type Ca(2+) channels is lacking. We investigated whether non-L-type Ca(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 mm K(+) ('basal' secretion) or 60 mm 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 mm) 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.

Gene Expression in the Hippocampus in a Rat Model of Premenstrual Dysphoric Disorder After Treatment With Baixiangdan Capsules

“…The types and their physiological functions differ in different tissue cells and different parts of the same cell ( Spedding and Paoletti, 1992 ). The physiological functions include calcium homeostasis maintenance ( Nayler and Sturrock, 1986 ), control of muscle contraction ( Held et al, 2007 ), release of neurotransmitters ( Miki et al, 2013 ), promotion of cell growth and proliferation, regulation of hormone secretion ( Sosial and Nussinovitch, 2015 ), and influences on gene expression ( Doran et al, 2007 ). Cacna1a, a P/Q type of voltage-dependent calcium channel located in nerve cell membranes, is widely distributed in the neuromuscular junction, and mainly participates in mediating the release of certain neurotransmitters ( Catterall, 1998 ).…”