Biochemical evidence for cholinergic innervation of intracerebral blood vessels

Muscarinic cholinergic receptor sites were detected with [3H]quinuclidinylbenzilate (QNB) binding techniques in two fractions of bovine intracerebral vessels; one of the fractions contained primarily small arteries and veins with some attached capillaries, and the other one was highly enriched in capillaries. The amounts of binding were similar in equivalent vascular fractions isolated from cerebral cortex, caudate nucleus and cerebellar cortex in spite of large differences among the 3 regions in [3H]QNB binding to brain tissue. The different distribution of muscarinic receptors in brain tissue and blood vessels argues against the possibility that the receptors represent a contamination of the vascular fractions by brain parenchyma. Cerebral endothelial cells, which were isolated by treating capillaries with collagenase, bound [3H]QNB to the same extent as did cerebral capillaries. This is consistent with an endothelial localization of capillary muscarinic receptors. Choline acetyltransferase (ChAT) activity, a marker for cholinergic neurons, also was present in the vascular preparations. Within each brain region, ChAT activities in capillaries and larger vessels were similar, but significant regional differences were found for vascular ChAT activity, with the highest values in the caudate. Isolated endothelial cells contained significantly lower levels of ChAT activity than intact capillaries, suggesting a periendothelial location of the enzyme, as would also be the case for attached nerve terminals. The presence of [3H]QNB binding sites and ChAT activity in intracerebral blood vessels is consistent with an innervation of the cerebral vasculature by a cholinergic system that may regulate cerebral blood flow and capillary permeability.