A. Golard et al., SUBSTANCE-P POTENTIATES CALCIUM-CHANNEL MODULATION BY SOMATOSTATIN INCHICK SYMPATHETIC-GANGLIA, Journal of neurophysiology, 72(6), 1994, pp. 2683-2690
1. The whole cell patch clamp was used to measure calcium current in i
solated chick sympathetic ganglion neurons. Previous results showed th
at somatostatin inhibits calcium currents (I-Ca) in a voltage-dependen
t manner. The effect of somatostatin rapidly desensitizes. In addition
, the action of somatostatin on the calcium current is inhibited by ac
tivation of protein kinase C (PKC). Because substance P (SP) has been
shown to activate PKC in the chick sympathetic neurons, we here test t
he effects of SP on the calcium current and on the modulatory action o
f somatostatin. 2. At a concentration of 1 mu M, SP had small, variabl
e effects on I-Ca. 3. SP in the presence of guanosine 5'-triphosphate-
gamma-S, or at higher concentrations (10 mu M), inhibited I-Ca in a vo
ltage-dependent manner, similar to the action of somatostatin. 4. Rath
er than inhibiting the action of somatostatin, SP (1 mu M) potentiated
the response to somatostatin. This effect of SP was only observed aft
er the response to somatostatin had partially desensitized. SP had no
effect on nondesensitized responses to somatostatin. 5. Desensitizatio
n of the somatostatin response involved a shift in its dose-response c
urve toward higher somatostatin concentrations as well as a decrease i
n the maximal response. SP appears to counteract the shift of the dose
-response curve selectively. 6. The potentiation of the somatostatin r
esponse by SP is blocked by 1-(5-isoquinolinylsulfonyl)-2-methylpiperz
ine (H-7), but not by Calphostin C, Compound 5, k252a, protein kinase
C (PKC)(19-36), or adenylyl-imidodiphosphate (AMP-PNP), suggesting tha
t phosphorylation is not involved and that the H-7 action does not dep
end on kinase inhibition. 7. The action of SP does not appear to invol
ve dephosphorylation either, because its action was not blocked by the
phosphatase inhibitors calyculin A or okadaic acid. 8. These results
suggest a novel mechanism for interactions between two neurotransmitte
rs in which one transmitter potentiates the action of a second by coun
teracting the effects of desensitization.