[Value of new agonists of the acinar and ductal phases of exocrine secretions].
Exocrine secretions proceed in two phases which can be studied individually in submandibular glands. We have investigated the response to neuropeptides and purinergic agonists of rat submandibular glands. Pituitary Adenylate Cyclase Activating Peptide (PACAP), an analog of VIP increased the intracellular concentration of cyclic AMP in acinar cells. PACAP also stimulated the activity of the Na(+)-K(+)-2Cl(-)-cotransporter. Extracellular ATP increased the [Ca2+]i in ductal cells. Two distinct receptors were involved in this response. A metabotropic purinergic receptor of the P2Y1 type raised the cellular concentration of IP3 after activating a phospholipase C. The second component of the purinergic response involved an ionotropic P2X7 receptor. After binding an agonist, this receptor formed a non-specific cation channel permeant to calcium and manganese, highly sensitive to inhibition by nickel. Two phospholipases A2 were activated following the occupancy of this receptor. The calcium-independent enzyme triggered kallikrein secretion in response to extracellular ATP. In conclusion, neuropeptides and purinergic agonists activate the acinar and ductal phases of the salivary secretion and are therefore promising candidates for the development of new sialagogues for therapeutic use.
Dehaye
J P
JP
Service de Biochimie générale et humaine, Université libre de Bruxelles.
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D009479:Neuropeptides / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D058913:Purinergic Agonists; D051381:Rats; D028021:Sodium-Potassium-Chloride Symporters; D013363:Submandibular Gland / Q000187:drug effects* / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives; D014987:Xerostomia / Q000188:drug therapy
C495403:Adcyap1 protein, rat; D002352:Carrier Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D058913:Purinergic Agonists; D028021:Sodium-Potassium-Chloride Symporters; D014660:Vasoactive Intestinal Peptide