30 A

C 18 A Latency in the Activation of Lipolysis in Adipose Tissue during Nerve Stimulation

By B. B. FREDHOLM. Department of Pharmacology, Karolinska Institutet, Stock- holm, Sweden

Following stimulation of the nervous supply to canine subcutaneous adipose tissue an increased rate of free fatty acid (FFA) and glycerol release is observed (Rosell 1966, Fredholm and Rosell 1968). The increased release rate is not seen immediately upon the start of the stimulation and the highest release rates generally occur after the cessation of the stimulation. This pattern of response is changed by adrenergic a-receptor antagonists e.g. dihydroergotamine: the rate of glycerol and FFA release increases rapidly upon nerve stimulation and the highest release rates are generally seen during the stimulation period. Moreover, the amount of FFA and glycerol released is higher after a-blockade (Fredholm and Rosell 1968).

There were essentially three different possibilities to explain these findings: 1. Stimulation of adrenergic a-receptors counteracts the lipomobilizing effect of adren- ergic /&receptor stimulation. 2. The lipolytic process starts immediately upon the initiation of nerve stimulation, but the outflow of the products of lipolysis is delayed owing to trapping in the tissue secondary to vasoconstriction. 3. Not only the outflow of lipolytic products but the activation of lipolysis is also delayed.

The first possibility was tested in six experiments where the rate of glycerol and FFA release was increased by theophylline (Fredholm 1970) and the /?-receptors inhibited by propranolol (400 mg i.a.). During nerve stimulation after this pretreat- ment there was a decreased glycerol outflow, but after cessation of the stimulus a transient increase was observed. There was no net effect of the nerve stimulation in- dicating that there is no significant inhibition of lipolysis by adrenergic a-stimula- tion.

In an attempt to discriminate between the two remaining possibilities a series of eight experiments were carried out. Two consequtive nerve stimulations (4 cps for 20 min) were applied. During the second propranolol was given after 12 min. If the animals were pretreated with dihydroergotamine the second nerve stimulation caused the release of 89 f 23 per cent of the first. If on the other hand no pretreat- ment was given the figure was 34f 12 per cent. I t can be concluded that if the adrenergic a-receptors are intact significantly smaller lipolysis occurred during the first part of the stimulation compared to the latter.

The results thus demonstrate a latency in the activation of lipolysis during nerve stimulation in canine subcutaneous tissue. I t is conceivable that a severed transport of the adrenergic transmitter substance from nerve ending to fat cell is the underly- ing cause. (Fredholm and Rosell 1970).

References FREDHOLM, B. B., Acta pharrnacol. 1970. 28. Suppl. 1.47. FREDHOLM, B. and S. ROSELL, J . Pharmacol. exp . Ther. 1968. 159. 1-7. FREDHOLM, B. B. and S. ROSELL, Acta physiol. scand. 1970. 80. 404-411. ROSELL, S., Acta physiol. scand. 1966. 67. 343-351.