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Phospholipase C activation and Ca2+ mobilization by cloned human somatostatin receptor subtypes 1-5, in transfected
1Department of Physical Biochemistry, Gunma University, Maebashi, Japan.
Abstract:
We transfected the COS-7 cells with cDNAs encoding different human somatostatin receptor (hSSTR) subtypes, and found that hSSTR subtypes mediate not only the inhibition of forskolin-induced cAMP accumulation but also the stimulation of phospholipase C (PLC) and Ca2+ mobilization. Activation of PLC by 1 microM somatostatin (SRIF) was in the order of: hSSTR5 > hSSTR2 > hSSTR3 > hSSTR4 >> hSSTR1. Pertussis toxin (PTX) treatment completely or partially reversed the PLC activation. 1 nM SRIF was equally effective for adenylate cyclase (AC) inhibition in a PTX-sensitive manner, in all the cells expressing different hSSTRs, except for hSSTR1. Nevertheless, SRIF stimulated AC even in the presence of forskolin at higher doses of SRIF in PTX-treated hSSTR5-expressing cells. We conclude that the cloned hSSTRs differentially couple to PTX-sensitive and -insensitive G-proteins to modulate PLC, Ca2+ mobilization and AC.
Insights
Human somatostatin receptors (hSSTRs) modulate cell signaling pathways, including cAMP, phospholipase C (PLC), and Ca2+ mobilization. These receptors differentially couple to G-proteins, influencing cellular responses.
Area of Science:
- Molecular Pharmacology
- Cell Signaling
- G Protein-Coupled Receptors
Background:
- Human somatostatin receptors (hSSTRs) are G protein-coupled receptors involved in various physiological processes.
- Understanding the signaling pathways modulated by different hSSTR subtypes is crucial for therapeutic development.
Purpose of the Study:
- To investigate the signaling pathways mediated by distinct human somatostatin receptor (hSSTR) subtypes.
- To elucidate the coupling of hSSTRs to pertussis toxin (PTX)-sensitive and -insensitive G-proteins.
Main Methods:
- Transfection of COS-7 cells with cDNAs encoding different hSSTR subtypes.
- Measurement of cyclic AMP (cAMP) accumulation, phospholipase C (PLC) activation, and Ca2+ mobilization.
- Assessment of the effects of somatostatin (SRIF) and PTX treatment on signaling pathways.
Main Results:
- hSSTR subtypes inhibited forskolin-induced cAMP accumulation and stimulated PLC and Ca2+ mobilization.
- PLC activation by SRIF followed the order: hSSTR5 > hSSTR2 > hSSTR3 > hSSTR4 >> hSSTR1.
- PTX treatment reversed PLC activation, indicating involvement of PTX-sensitive G-proteins. Adenylate cyclase (AC) inhibition was PTX-sensitive for all hSSTRs except hSSTR1.
Conclusions:
- Cloned hSSTRs differentially couple to PTX-sensitive and -insensitive G-proteins.
- hSSTRs modulate PLC, Ca2+ mobilization, and AC activity through distinct G-protein signaling pathways.
- These findings highlight the complex signaling networks regulated by somatostatin receptors.