Ultrastructural localization of cholinergic muscarinic receptors in rat brain cortical capillaries

Cholinergic innervation of the cerebrovasculature is known to regulate vascular tone, perfusion rate and permeability of the microvascular wall. Notably the cholinergic innervation of cerebral capillaries is of interest since these capillaries form the blood-brain barrier. Although there is a general consensus as to the presence of nicotinic and muscarinic receptors in the domain of the capillary wall, their precise anatomical position is unknown. The subcellular localization of muscarinic receptors in rat cortical capillaries was approached by way of immunocytochemistry at the ultrastructural level using monoclonal antibody M35 against muscarinic receptor protein. Binding of this antibody in the microvascular domain was found in 5% of the capillaries studied and was exclusively present in perivascular astroglia, and never in endothelium or pericytes. Combined with reported data on presynaptic cholinergic innervation the results indicate a cholinergic innervation pattern of non-directed presynaptic terminal structures in apposition to cholinoceptive perivascular astroglia with muscarinic receptor positive endfeet embracing the capillary basement membrane. The possible functional significance of such a cholinergic vascular innervation pattern is discussed with respect to capillary dynamics and barrier function.