Low affinity purinergic receptor modulates the response of rat submandibular glands to carbachol and substance P

M. Métioui, H. Amsallem, E. Alzola, N. Chaib, A. Elyamani, A. Moran, A. Marino, J. P. Dehaye

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


The effect of extracellular ATP on the intracellular calcium concentration ([C2+](i)) in rat submandibular glands was tested. The dose-response curve for ATP was biphasic with a first increase in the 1-30 μM concentration range and a further increase at concentrations higher than 100 μM. Among ATP analogs, only benzoyl-ATP stimulated the low affinity component. ATPτS blocked this response. All the other analogs tested reproduced the high-affinity low capacity response. Magnesium and Coomassie blue selectively blocked the low affinity component. High concentrations of ATP blocked the increase of the intracellular calcium concentration [Ca2+](i) in response to 100 μM carbachol. By itself, substance P (100 pM-1 μM) increased the [Ca2+](i). One mM ATP potentiated the response to concentrations of substance P higher than 10 nM. This potentiation was reversed by extracellular magnesium. Carbachol 100 μM and substance P (100 PM-1 μM) increased the release of inositol trisphosphate (IP3) from polyphosphoinositides (polyPI). Activation of the low affinity ATP receptors did not activate the polyPI-specific phospholipase C but inhibited its activation by 100 μM carbachol (-50%) and by 100 nM substance P (-60%-at 1 nM substance P and -40% at 100 nM substance P). Substance P induced a strong homologous desensitization: a preincubation with 1 nM substance P nearly completely abolished the response to 1 μM substance P. When the cells were exposed to ATP before the second addition of substance P, the purinergic agonist partially restored the response to the tachykinin without totally reversing the desensitization. It is concluded that two types of purinergic receptors coexist in rat submandibular glands; a high-affinity, low capacity receptor which remains pharmacologically and functionally undefined and a low affinity site, high capacity receptor of the P(2Z) type coupled to a non-selective cation channel. The occupancy of these low affinity sites blocks the increase of the [Ca2+](i) in response to a muscarinic agonist and the activation of polyPI-specific phospholipase C by carbachol and substance P. It potentiates the effect of high concentrations of substance P on the [Ca2+](i).

Original languageEnglish
Pages (from-to)462-475
Number of pages14
JournalJournal of Cellular Physiology
Issue number2
StatePublished - 1 Aug 1996

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


Dive into the research topics of 'Low affinity purinergic receptor modulates the response of rat submandibular glands to carbachol and substance P'. Together they form a unique fingerprint.

Cite this