Muscarinic cholinergic receptors on murine lymphocyte subpopulations. Selective interactions with second messenger response system upon pharmacological stimulation.
In this study the muscarinic cholinergic receptor capacity and affinity in murine lymphocyte sets and subsets and the biochemical responses obtained by the pharmacological stimulation of cholinergic receptors in these cells was determined by means of binding studies. Saturation assays with the specific radioligand for muscarinic cholinergic receptors ([3H]QNB) showed that B lymphocytes lack high affinity muscarinic cholinergic receptors, while the binding on T cells was a specific and saturable process. Lyt 2.2+ cells have a significantly higher number of receptors (Bmax) than L3T4+ cells; but the equilibrium dissociation constant (Kd) values obtained in both subpopulations did not differ significantly from one another, and resembled the Kd value of T lymphocyte populations. The specific receptor stimulation by carbachol caused a different intracellular signal transduction according the tested cell subtypes. The muscarinic cholinergic stimulation result in a significant inhibition of isoproterenol-stimulated adenylate cyclase system in T, L3T4+ and Lyt 2.2+ cells. On the contrary, Lyt 2.2+ cells were only able to respond to carbachol stimulus increasing cGMP levels and inositol phosphate formation while L3T4+ cells were unable to do it. Results show differences in the expression and in the ability of cholinergic receptors in sets and subsets of murine lymphocytes to trigger intracellular second-messenger systems. The differential receptor expression and the second-messenger response systems could be important to study the modulation of cellular immune response by cholinergic stimulation.
Genaro
A M
AM
Centro de Estudios Farmacologicos y Botanicos (CEFYBO), Concejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires, Argentina.
Cremaschi
G A
GA
Borda
E S
ES
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010716:Phosphatidylinositols / Q000378:metabolism; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D002217:Carbachol; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol