Muscarinic binding of pial vessels and arachnoid membrane.
The muscarinic sites in arachnoid and pial vessels were compared by analysis of the binding of quinuclidinyl benzilate (QNB) to membrane preparations. Saturation analysis indicated that the process was saturable, high affinity, and related to protein concentration in both structures. Although the affinities in the two structures [KD = 0.039 (arachnoid) and 0.097 nM (pial vessels)] were similar, the arachnoid had approximately 10-fold more binding sites (Bmax = 2,100 fmol/mg of protein) than the pial vessels (Bmax = 250 fmol/mg of protein). This difference was found in both bovine and porcine fractions. Pharmacological analysis of [3H]QNB displacement by muscarinic and nonmuscarinic ligands gave the typical pattern of muscarinic receptors in both structures. Inhibition of binding to pial vessels by the M1 antagonist pirenzepine revealed only one low-affinity site (Ki = 7.8 x 10(-7) M), whereas, the arachnoid had a small proportion (21%) of high-affinity sites (Ki = 2.2 x 10(-9) M) associated with low-affinity sites (Ki = 5.50 x 10(-7) M). It is concluded that muscarinic-mediated effects that do not involve the M1 subtype are induced in bovine pial vessels by a relatively low concentration of binding sites. The high content of muscarinic binding sites and their diversity in the arachnoid suggest a functional role for muscarinic cholinergic receptors in this structure.
Lasbennes
F
F
Laboratoire de Recherches Cérébrovasculaires (CNRS UA 641), Faculté de Médecine Villemin, UFR Lariboisière Saint-Louis, Université Paris VII, France.
Verrecchia
C
C
Philipson
V
V
Seylaz
J
J
D000818:Animals; D001099:Arachnoid / Q000098:blood supply* / Q000648:ultrastructure; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D002417:Cattle; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D009116:Muscarine / Q000378:metabolism*; D010841:Pia Mater / Q000098:blood supply* / Q000648:ultrastructure; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism / Q000502:physiology; D011976:Receptors, Muscarinic / Q000378:metabolism / Q000502:physiology; D013552:Swine; D014316:Tritium
D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D014316:Tritium; D011813:Quinuclidinyl Benzilate; D009116:Muscarine