Somatostatin Inhibits Basal and Vasoactive Intestinal Peptide-Stimulated Hormone Release by Different Mechanisms in GH Pituitary Cells^*

Abstract

Somatostatin (SRIF) inhibits both basal and vasoactive intestinal peptide (VIP)-stimulated hormone secretion by the GH4C1 clonal strain of rat pituitary tumor cells. We have previously shown that SRIF inhibits cAMP accumulation stimulated by VIP but does not alter basal cAMP levels in this cell line. To determine the importance of changes in cAMP accumulation in the mechanism of SRIF action, we have compared the effect of SRIF on hormone release stimulated by VIP and two other secretagogues which increase effective intracellular cAMP concentrations: forskolin and 8-Bromo-cAMP (8-Br-cAMP). VIP stimulated GH and PRL secretion to the same maximal extent (220% of control) with similar ED50 values (0.37 +/- 0.03 and 0.43 +/- 0.08 nM, mean +/- SE, respectively). SRIF (100 nM) reduced maximal VIP-stimulation of both GH and PRL release from 220 to 140% of control; however, it did not significantly change the ED50 values for VIP. The effect of SRIF on VIP-stimulated hormone release parallels its action on VIP-stimulated cAMP accumulation. Furthermore, the concentrations of SRIF required to produce half-maximal inhibition of VIP-stimulated GH and PRL release (0.8 +/- 0.2 nM and 0.7 +/- 0.1 nM, respectively) were similar to its potency to inhibit VIP-stimulated cAMP accumulation (1.2 +/- 0.1 nM). These data indicate that changes in cAMP levels mediate inhibition of VIP-stimulated hormone secretion by SRIF. Forskolin increased cAMP accumulation with an ED50 value of 2.4 +/- 0.5 microM. A maximal concentration of forskolin (100 microM) stimulated cAMP accumulation to a greater extent than 100 nM VIP (34 +/- 4-fold vs. 9 +/- 1-fold). Together, forskolin (100 microM) and VIP (100 nM) stimulated cAMP accumulation by more than 50-fold. However, PRL secretion in response to maximal concentrations of VIP or forskolin individually or together were the same (approximately 200% of control). These results support the conclusion that both compounds stimulate PRL secretion by a cAMP-mediated mechanism which can be fully activated by either one alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Somatostatin inhibits VIP‐ and isoproterenol‐stimulated cyclic AMP accumulation in rat prostatic epithelial cells

“…Therefore, the present results in rat prostatic epithelial cells suggest the existence of somatostatin receptors coupled to adenylate cyclase in an inhibitory manner, probably through a guanosine nucleotide-binding protein [13]. However, further studies are required to understand the precise role of cyclic AMP in the action of somatostatin at this level since a cyclic AMPindependent mechanism may also be involved in some somatostatin effects in various tissues [7]. Finally, the exact nature of somatostatin receptors in prostatic epithelium remains to be established since biologically active somatostatin receptors appear to exist in both plasma membrane and intracellularly in various systems [14].…”

“…Somatostatin is a well known inhibitor of cyclic AMP synthesis stimulated by a number of agents including VIP [7] and catecholamines [8] in other tissues. The present study examined the action of somatostatin, both alone or in combination with VIP and the /Y-adrenergic agonist isoproterenol, upon cyclic AMP accumulation in isolated epithelial cells of rat ventral prostate.…”

Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney.

“…Although both possess a similar affinity for somatostatin-14 and -28, their sequences are surprisingly divergent. This sequence divergence may well underlie the diverse biological effects of somatostatin (2) by coupling its receptors to different intracellular effector systems (27,28). The cloning of SSTR1 and SSTR2 should lead to a better understanding of the molecular basis for SSTR heterogeneity as determined by cross-linking analyses (29)(30)(31)(32) and the mechanisms and regulation of somatostatin function.…”

The Interactive Effects of VIP, PHI, GHRH and SRIF on the Release of Growth Hormone from Cultured Adenohypophysial Cells in Cattle.

“…GHRH and VIP are known to exert their actions through the activation of CAMP [2,21], whereas SRIF may exert its effects on GH secretion by interfering with cAMP production or by an action on the secretory process subsequent to CAMP production in rats [23]. It has also been reported that VIP directly stimulates somatotrophs and that the effect seems to imply a coupling of VIP receptors with cAMP production in rats [6], and the SRIF-induced inhibition of VIP-stimulated GH release from rat pituitary tumor cells is closely coupled to the inhibition of VIP-stimulated CAMP accumulation [27]. Since amino acid sequences are considerably overlapped between VIP and GHRH [1], VIP may exhibit 'GRF-like' activity under physiological condition [11].…”