Somatostatin alters beta-adrenergic receptor-effector coupling in cultured rat astrocytes.

Abstract

The neuropeptide somatostatin potentiates beta‐adrenergic receptor‐mediated cAMP formation in astrocytes derived from neonatal rat cortex but does not affect cAMP levels by itself. beta‐Adrenergic receptors in these cells can be specifically labeled with the high affinity antagonist [125I] cyanopindolol ([125I]CYP). In addition, astrocytes display both high and low affinity binding sites for the agonist isoproterenol, which are thought to represent receptors which are coupled or uncoupled, respectively, to the guanine nucleotide regulatory protein. We find that somatostatin does not modify beta‐receptor density, nor receptor affinity for either the antagonist ([125I]CYP) or for the agonist isoproterenol. In the presence of the guanine nucleotide analogue, Gpp(NH)p, only low affinity (uncoupled) displacement of [125I]CYP binding by isoproterenol is observed. However, somatostatin (1 microM), when added to the cells together with Gpp(NH)p, prevents the nucleotide‐induced loss of the high affinity (coupled) component of agonist displacement. This result suggests that somatostatin increases noradrenaline‐induced cAMP production by enhancing coupling between the beta‐receptor and the stimulatory guanine nucleotide regulatory protein.

Selective blockade of dopamine D-1 receptor by SCH 23390 affects dopamine agonist binding to 3H-spiperone labeled D-2 receptors in rat striatum.

“…In light of our existing knowledge that GTP decreases the affinity of the dopamine agonist for the D-2 receptor because of an association of G protein with the D-2 receptor, we therefore used IAP (a pertussis toxin) to inactivate GI which is involved in the D-2 inhibition of the enzyme adenylate cyclase. Generally, the IAP treatment could not completely inactivate GI, as shown by the fact that the D-2 mediated inhibition of adenylate cyclase was partially decreased and the ability of guanine nucleo tide to reduce the affinity of dopamine agonist for D-2 receptor was reduced, but not abolished following IAP treatment (5, 6, 30 (31,32) or the affinity of the agonist-receptor interaction (20,32), but in all cases, these regulatory effects are mediated by receptor agonists. On the basis of receptor-activation leading to the dis sociation of G-proteins whose subunits may interact with other receptor G-protein com plexes, it is easy to understand the speculation that G protein is involved in these cases.…”

Pathophysiology of GPCR Homo- and Heterodimerization: Special Emphasis on Somatostatin Receptors

“…Recent studies have shown direct evidence that SSTR subtypes functionally interact with β-ARs [37,40]. Previous studies as early as in 1985 pointed out this association and provided the evidence that β-AR mediated cAMP was enhanced in presence of SST in astrocytes prepared from rat brain without displaying any changes in β-AR binding properties [229]. Interestingly, in cultured astrocytes SST alone has no effect on cAMP.…”

Heterodimerization of β₂ adrenergic receptor and somatostatin receptor 5: Implications in modulation of signaling pathway

“…There is no direct evidence whether SSTR and β-AR subtypes functionally interact with each other. Although, as early as in 1985, a study has described that in rat brain astrocytes, SST enhanced the production of β-AR mediated cyclic adenosine monophosphate (cAMP) [31]. In addition, agonist occupied β-AR gets phosphorylated in presence of β-AR kinase and SST and isoproterenol displayed similar effect in promoting the translocation of β-AR kinase [32,33].…”