Choline acetyltransferase activity in the sympathetic nerves of the rabbit ear artery.

1 No statistically significant difference in the activity of choline acetyltransferase (ChAT) was detected between sympathetically denervated and control rabbit ear artery (REA) tissue. This was interpreted as evidence against the hypothesis that endogenous acetylcholine plays an obligatory role in sympathetic postganglionic neurotransmission. 2 The values obtained for ChAT activity in the extraneuronal REA tissue were very low, but were greater than the boiled blank values. 3 Treatment with a specific inhibitor of ChAT did not reduce the REA values, while it did for rabbit iris. Addition of acetylcholinesterase to the REA assay reduced the activity of the collectable product to a markedly lesser degree than was observed with other tissues. 4 The specificity of the enzyme assay at the very low yield levels observed in the extraneuronal REA tissue was therefore questioned.

Biochemical determinations of cholinergic innervation in cerebral arteries.

Endogenous choline acetyltransferase (ChAT) activity and high affinity (HA) 3H-choline uptake can be assayed specifically and used to quantify cholinergic neuronal mechanisms. In general, arteries at the base of the brain in the cat and rabbit were distinguished by high and in the dog by lower ChAT activity and 3H-choline levels of uptake. There was a linear relationship between the mean values of the observations from of the two assays on given cerebral arteries from the three species (r = 0.871,P less than 0.001). Since ChAT activity and HA 3H-choline uptake essentially are confined to cholinergic nerve terminals, our results imply that the Circle of Willis and its main branches in the cat, rabbit, and dog are cholinergically innervated.

The metabolism of (R)-(-)-amphetamine by rabbit liver microsomes. Initial products.

The metabolism of 1-amphetamine in rabbit liver is complex in that several routes may give rise to the same intermediate. In this study, the subsequent metabolism of the primary products of N- and C-oxidation were blocked by selecting appropriate incubation conditions. The resulting simplified system was used to investigate the enzymes involved in the two pathways. Phenobarbital treatment increased N- and C-hydroxylation, whereas 3-methylcholanthrene treatment had an inhibitory effect on both pathways. Inhibitors of cytochrome P-450 were either nonselective or were partially selective in inhibiting the two routes of amphetamine metabolism. Induction modulated the sensitivity toward the inhibitors of N- and C-oxidation.

Distribution of choline acetyltransferase in cerebral and extracerebral cranial arteries of the cat. Its relationship to neurogenic atropine-sensitive dilation.

Choline-acetyltransferase (ChAT) activity was surveyed in segments of cranial arteries--both cerebral and extracerebral--from the cat. High levels were found in pial arteries, both cerebral and cerebellar, and in the arteries to salivary glands, tongue, and nose. Intermediate levels were found in the external and internal maxillary arteries and many of their branches. Enzyme levels in the arteries supplying the head--common carotid, vertebral, and in several systemic arteries and veins and also the lingual vein--were probably not significant. Only those vessels that have higher ChAT contents show capacity for neurogenic vasodilation. The dilation of segments of a number of these arteries, the basilar, middle cerebral, lingual, and internal maxillary, is reduced significantly by atropine (5 X 10(-7) M). ChAT activity did not correlate with vessel norepinephrine content. The data may be interpreted as defining a functional vasodilator system to the head encompassing both cerebral and extracerebral arteries that depends in part on a functional cholinergic link involving a muscarinic receptor. It is separate from the adrenergic outflow. The tissues supplied by vasculature receiving this type of innervation are of ectodermal origin.

Specialization in cerebral and extracerebral neurovascular mechanisms.

The neuroeffector properties of four blood vessels with diverse characteristics are compared and contrasted. The variables include the density and distribution pattern of sympathetic innervation; size, direction, and nerve frequency-characteristics of the neurogenic response, nature of the sympathetic transmitter, receptor types, and receptor-response coupling; and the level and temperature sensitivity of myogenic tone. In many instances, these features can be related to the functional role of the vessels and their pharmacological characteristics. The underlying basis of this diversification, with one exception, which can be related to developmental origin, is entirely unknown.