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Somatostatin blocks a calcium current in rat sympathetic ganglion neurones.
Author(s) -
Ikeda S R,
Schofield G G
Publication year - 1989
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1989.sp017494
Subject(s) - somatostatin , endocrinology , medicine , chemistry , calcium , biophysics , biology
1. The effects of somatostatin and somatostatin analogues on a Ca2+ current from acutely isolated and short‐term (24‐48 h) cultured adult rat superior cervical ganglion (SCG) neurones were studied using the whole‐cell variant of the patch‐clamp technique. 2. [D‐Trp8]Somatostatin (SOM) produced a rapid, reversible and concentration‐dependent reduction of the Ca2+ current. Ca2+ current amplitude was reduced over the voltage range ‐15 to +40 mV with the greatest reduction occurring where the amplitude was maximal (ca +10 mV). In the presence of SOM, the Ca2+ current rising phase was slower and biphasic at potentials between 0 and +40 mV. 3. Application of 0.1 microM‐SOM for greater than 10 s resulted in a desensitization of the response. During a 4 min application of 0.1 microM‐SOM, Ca2+ current amplitude returned to about 90% of control. A second application of 0.1 microM‐SOM produced less block than the initial application. 4. Concentration‐response curves for SOM, somatostatin‐14 (SOM‐14) and somatostatin‐28 (SOM‐28) were fitted to a single‐site binding isotherm. The concentrations producing half‐maximal block and the maximal attainable blocks of the Ca2+ current for SOM, SOM‐14 and SOM‐28 were 3.3, 5.4 and 35 nM, respectively and 55, 51 and 54%, respectively. SOM‐14 and SOM‐28 slowed the Ca2+ current rising phase in a manner similar to that of SOM. Somatostatin‐28 had no effect on the Ca2+ current at 1 microM. 5. The magnitude of the Ca2+ current block produced by 0.1 microM‐SOM was not significantly altered in the presence of 1 microM‐idazoxan, atropine, naloxone or the somatostatin antagonist aminoheptanoyl‐Phe‐D‐Trp‐Lys‐O‐benzyl‐Thr. 6. Internal dialysis with solutions containing 500 microM‐guanylyl‐imidodiphosphate (Gpp(NH)p) or guanosine‐5'‐O‐(3‐thiotriphosphate)(GTP‐gamma‐S) decreased the Ca2+ current amplitude by 36 and 41%, respectively, and induced a biphasic rising phase in the Ca2+ current. Under these conditions, application of 0.1 microM‐SOM produced significantly less block of Ca2+ current amplitude (7.1 and 14.7%, respectively) when compared with controls. 7. Internal dialysis with solutions containing 500 microM‐guanosine‐5'‐O‐(2‐thiodiphosphate)(GDP‐beta‐S) had no significant effect on either the Ca2+ current amplitude or block produced by 0.1 microM‐SOM. 8. Internal dialysis with solutions containing 500 microM‐cyclic adenosine 3',5'‐monophosphate (cyclic AMP) and 3‐isobutyl‐1‐methylxanthine had no significant effect on either the Ca2+ current block produced by 0.1 microM‐SOM or the Ca2+ current amplitude.(ABSTRACT TRUNCATED AT 400 WORDS)