Characterization of voltage operated R-type Ca2+ channels in modulating somatostatin receptor subtype 2- and 3-dependent inhibition of insulin secretion from INS-1 cells.

Somatostatin inhibits Ca(2+) entry into pancreatic B-cells via voltage-operated Ca(2+) channels (VOCCs) of L-type, leading to the suppression of insulin secretion. Activation of R-type channels increases insulin secretion. However, the role of R-type Ca(2+) channels (Ca(V)2.3) in mediating the effects of on insulin secretion has not been so far investigated. Here, we identify the subtypes expressed on insulin-producing INS-1 cells by RT-PCR and by functional assays. The role of R-type channels in regulating [Ca(2+)](i) in response to was detected by cell fluorescence imaging and patch-clamp technique. INS-1 expressed and and agonists (ag.) selective for these receptors reduced 10 nM exendin-4/20 mM glucose-stimulated insulin secretion. Surprisingly, duanyu1942 and transiently increased [Ca(2+)](i). Subsequently, these agonists led to a decrease in [Ca(2+)](i) below the basal levels. In contrast, failed to induce a transient peak of [Ca(2+)](i). Instead, a persistent minor suppression of [Ca(2+)](i) was detected from 25 min. R-type channel blocker SNX-482 altered [Ca(2+)](i) in and cells. Notably, the inhibition of insulin secretion by duanyu1942 and but not duanyu19423-ag. was attenuated by SNX-482. Taken together, duanyu1942 and duanyu1942R2 regulate [Ca(2+)](i) and insulin secretion in INS-1 cells via R-type channels. In contrast, the R-type calcium channel does not mediate the effects of duanyu19423-ag. on insulin secretion. We conclude that R-type channels play a major role in the inhibition of insulin secretion by somatostatin in INS-1 cells.

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