Glucagon (Glu) influences renal tubular function and growth, although the sigal transduction of Glu in the kidney still remains obscure. Rabbit cortical tubules were transformed by the pSV-neo3 gene to make a homogeneous cell colony, which responded to vasopressin but not to parathyroid hormone. The [Ca
2+]i of the cells at the 9-10th passages was measured by the fluorescence indicator, fura-2. The [Ca
2+]i was increased by Glu (10
-8 M) or bradykinin (10
-8 M), between which heterologous desen sitization was observed. The Glu range of 10
-14 to 10
-6 M significantly increased [Ca
2+]i, while CAMP was not produced at any dose of Glu. Since the ranges of doses were from physiological to pharmaco logical, two concentrations of 10
-13 and 10
-8 M were employed to investigate the mechanisms . Glu at 10
-13 M led to a sustained rise in [Ca
2+]i, which was completely blocked by external EGTA (5 mM, Ca-free solution). Glu at 10
-8 M provided a similar level of peak and sustained rise in [Ca
2+]i, the sustained phase of which was blunted in Ca-free solution. Inositol tri/tetra phosphates were significantly increased by 10
-8 M, but not by 10
-13M Glu. These data suggest that [Ca
2+]i elevation is a major component of Glu-induced second messengers in the physiological and pharmacological range of doses of Glu, and that there might be two classes of pathways leading to increase in [Ca
2+]i in transformed rabbit cortical collecting tubule cells.
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