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- Title
Reversal of somatostatin inhibition of AVP-induced cAMP by pertussis toxin.
- Authors
Ishikawa, San-E.; Saito, Toshikazu; Kuzuya, Takeshi
- Abstract
The effect of somatostatin on the stimulation of adenosine-3′,5#x2032;-cyclic monophosphate (cAMP) production by arginine vasopressin (AVP) was examined in rat renal papillary collecting tubule cells in culture. The presence of phosphodiesterase inhibitor 3-isobutyl-1-methylxatathine AVP at a concentration of 1 ⊗ 10-10 M or higher significantly increased cellular cAMP levels in a dose-dependent manner. The stimulation by AVP of cellular cAMP production was significantly attenuated by 1 ⊗ 10-6 M somatostatin (1 ⊗ 10-9 M AVP. 477.5 ± 23.0 vs. 292.4 ± 28.5 fmol/μg protein per 10 min, P < 0.01). When the cells were pretreated with pertussis toxin, pertussis toxin completely abolished the inhibitory effect of somatostatin on cellular cAMP production in response to AVP. Such an effect was obtained with a concentration of 0.1 ng/ml or higher of pertussis toxin and an incubation time of longer than an hour. The exposure of cells to 100 ng/ml pertussis toxin for two hours recovered the cellular cAMP response to 1 ⊗ 10-9 M AVP in the presence of 1 ⊗ 10-6 M somatostatin, the value of which 527.1 ± 32.6 fmol/μg protein per 10 minutes, was a comparable level to that in response to only 1 ⊗ 10-9 M AVP. Also, somatostatin inhibited the cellular cAMP response to glucagon and cholera toxin, but did not inhibit basal and forskolin-stimulated cAMP levels. Pertussis toxin treatment of cells completely abolished these inhibitory effects of somatostatin. Since it is known that pertussis toxin ADP-ribosylates a 41,000 dalton subunit of guanine nucleotide binding protein (Ni): the present results therefore indicate that the inhibition by somatostatin of AVP-induced cellular cAMP production is mediated via Ni to properly couple inhibitory receptors to adenylate cyclase.
- Subjects
SOMATOSTATIN; ADENOSINES; RENAL papilla; KIDNEY tubules; PERTUSSIS toxin; ADENYLATE cyclase
- Publication
Kidney International, 1988, Vol 33, Issue 2, p536
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1988.31