Inositol trisphosphate-linked calcium mobilization couples substance P receptors to conductance increase in a rat pancreatic acinar cell line.
The action of substance P (SP) on a rat pancreatic acinar cell line, AR4-2J, was examined using the whole-cell voltage-clamp technique. Pressure application of SP evoked inward currents accompanying increased membrane conductance. The SP-induced response was suppressed in Ca2+-free or low-Na+ solution. Treatment of cells with caffeine or A23187 produced a transient inward current and depressed the response to SP. Intracellular application of inositol 1,4,5-trisphosphate or guanosine 5'-O-(3-thiotriphosphate) elicited sustained inward currents and suppressed the SP-induced response. The results suggest that activation of SP receptors stimulates the formation of inositol phosphates via a guanine nucleotide-binding protein and leads to the rise in intracellular Ca2+, thereby activating a cation conductance in AR4-2J cells.
Song
S Y
SY
Laboratory of Cellular Physiology, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Iwashita
S
S
Noguchi
K
K
Konishi
S
S
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002460:Cell Line; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000378:metabolism / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*; D013403:Sugar Phosphates / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology
D007295:Inositol Phosphates; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013403:Sugar Phosphates; D013873:Thionucleotides; D013373:Substance P; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000001:Calcimycin; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D002118:Calcium