The neuronal and extraneuronal uptake and deamination of 3H-(?)-phenylephrine in the perfused rat heart

Abstract

The neuronal and extraneuronal uptake and deamination of 3H-(-)-phenylephrine was studied in perfused rat hearts obtained from reserpine-pretreated animals. 1. Under the conditions of steady-state perfusion with 5 mumol/l 3H-(-)-phenylephrine slightly more than 50% of total deamination took place in adrenergic nerve endings, slightly less than 50% in the extraneuronal tissue. 2. 3H-(-)-phenylephrine is preferentially deaminated to the glycol metabolite. 3. There is pronounced non-saturable, cocaine- and corticosterone-resistant uptake of 3H-(-)-phenylephrine in the perfused rat heart. 4. The apparent rate constants for the efflux of the glycol metabolite is about 20 times higher than that for the efflux of the acid metabolite. 5. For both the glycol and the acid metabolite of 3H-(-)-phenylephrine, apparent rate constants for the efflux declined when the duration of the perfusion with the labelled parent amine was prolonged. This phenomenon was also observed when the deamination of 3H-(-)-phenylephrine was restricted to either the adrenergic nerve endings or the extraneuronal tissue. These results are interpreted as evidence for a distribution of each metabolite into at least two kinetically different compartments. 6. This was confirmed for the acid metabolite by determination of a biphasic efflux curve in wash-out experiments in which MAO was inhibited during wash-out (after an initial loading of the adrenergic nerve endings with 3H-(-)-phenylephrine).

Differences in sensitivity of rat mesenteric small arteries to agonists when studied as ring preparations or as cannulated preparations

“…Values show mean ± s.e.mean. Two experiments on the wire-myograph provided indirect verification that PE was also taken up by the nerves, as observed in other preparations (Rawlaw et al, 1980). After blocking reuptake with 3 gM cocaine, pECm-values for PE increased 0.58 and 0.44, respectively.…”

Age‐Related Changes in Aldehyde Dehydrogenase Activity of Rat Brain, Liver, and Heart

“…The concentrations of these aldehydes are controlled by the activities of aldehyde-metabolising enzymes (Duncan and Sourkes, 1974). However, important species differences have been observed: man seems to differ from the commonly used laboratory animals, particularly the rat, in forming very little glycol metabolites from NA and related compounds, since acid metabolites predominate in human urine (Rawlow et al, 1980;Davis et al, 1980).…”

Transient supersensitivity to α‐adrenoceptor agonists, and distinct hyper‐reactivity to vasopressin and angiotensin II after denervation of rat tail artery

“…We have assessed the relative contributions of changes in smooth muscle sensitivity to selective a 1-and a2-adrenoceptor agonists (phenylephrine, methoxamine and clonidine) and of loss of NETs to the hyper-reactivity of the artery 2 and 7 weeks after denervation. To assess the effects of losing NETs, we compared the effects of phenylephrine, which is a substrate for the NET (Rawlow et al, 1980), in the absence and in the presence of the NET inhibitor, desmethylimipramine. To assess changes in smooth muscle sensitivity to a1-and a2-adrenoceptor agonists, we used methoxamine and clonidine, respectively; methoxamine is not a substrate for the NET (Trendelenburg et al, 1970).…”