Characterization of muscarinic receptors in salivary and lacrimal glands of the rat.
The binding characteristics of muscarinic receptors in rat salivary and lacrimal glands were studied by means of radioligand binding techniques. In competition experiments against [3H]N-methylscopolamine, classical muscarinic antagonists ipratropium bromide, N-methylscopolamine and N-methylatropine exhibited very similar KD values in all the glands and their binding behavior was well described by a one binding site model (nH congruent to 1). The novel cardioselective antimuscarinic compound, AF-DX 116, displayed an equally low affinity in all the tissues examined. Pirenzepine and dicyclomine, two other selective muscarinic antagonists, showed a similar behaviour in all but the sublingual gland, where their binding profile indicated the presence of a heterogeneous receptor population (nH = 0.74 and 0.84, respectively). Histological studies of the sublingual-submandibular glandular complex demonstrated the presence of ganglionic structures mainly located in the hilum of the sublingual-submandibular glandular complex connected with the sublingual gland. Binding studies carried out with pirenzepine on the hilum and on a synaptosomal preparation from this region again revealed the presence of two populations of muscarinic receptors with KD values of 22-25 and 270-463 nM. These results are best explained by the presence of M1 and M2 receptors located on neuronal and glandular structures.
Department of Pharmacology, Faculty of Medicine, Malaga University, Spain.
F
F
Martos
E
E
Monferini
E
E
Giraldo
A M
AM
De Paoli
R
R
Hammer
D000818:Animals; D001286:Atropine Derivatives; D004025:Dicyclomine; D005088:Exocrine Glands / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007765:Lacrimal Apparatus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019832:N-Methylscopolamine; D010890:Pirenzepine / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012469:Salivary Glands / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D012602:Scopolamine Derivatives; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D001286:Atropine Derivatives; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D010890:Pirenzepine; D004025:Dicyclomine; C006649:methylatropine; C048593:otenzepad; D019832:N-Methylscopolamine