Adenylate cyclase of human fat cell ghosts. Stimulation of enzyme activity by parathyroid hormone.

Abstract

A B S T R A C T Some of the effects of native bovineparathyroid hormone and of the synthetic aminoterminal 1-34 fragment on the adenylate cyclase activity of human fat cell ghosts were studied. Saturating concentrations of both hormone preparations caused a significant increase of enzyme activity by about 200-300%. Guanosine 5'-triphosphate (0.1 mM) inhibited basal enzyme activity but had no substantial effect on parathyroid hormone-stimulated enzyme activity. The guanosine 5'-triphosphate analogue, 5'-guanylyl-imidodiphosphate, produced about a threefold enhancement of basal and parathyroid hormone-stimulated enzyme activities under standard conditions (5 mM Mg2+, 1 mM ATP, pH 8.0, 30°C).Activation by parathyroid hormone was not influenced by 83-adrenergic blockade in contrast to stimulation by epinephrine. The sensitivity of the enzyme system to the native and the synthetic parathyroid hormone was, however, abolished after pretreatment of the fat cells with trypsin (1 mg/ml). The stimulatory effects of epinephrine and NaF were not affected by pretreatment with trypsin.The results suggest that human fat cells, like rat adipocytes, contain a multireceptor-coupled adenylate cyclase.

Biphasic effects of prostaglandin E2 on the human fat cell adenylate cyclase.

“…Experimental procedures were the same as described, (8). Fat cells and fat cell ghosts were prepared according to Rodbell (9).…”

Adenylate cyclase of human fat cell ghosts

“…Experimental procedures were essentially the same as in [6] . Fat cells and fat cell ghosts were prepared according to [lo] .…”

Effects of some naturally occurring prostaglandins of the D-, E-, and I-type and synthetic analogues on adenylate cyclase of human fat cell ghosts

“…Experimental procedures were the same as described previously [10]. Fat cells and fat cell ghosts were prepared according to Rodbell [15].…”

“…Since prostaglandins are synthesized in response to lipolytic hormones [4,5], feed-back inhibition of the adenylate cyclase has been proposed as the mechanism underlying the antilipolytic effects of these C-20 fatty acids [1]. As opposed to this concept, we have recently found that prostaglandins of the E-and 0300-9130/79/0176/0025/$ 1.00 F-type are potent activators of the h u m a n fat cell adenylate cyclase [9]. In terms of the negative feed-back concept the physiological meaning of these findings a p p e a r e d to be difficult to assess.…”

“…In terms of the negative feed-back concept the physiological meaning of these findings a p p e a r e d to be difficult to assess. Since the h u m a n fat celt adenylate cyclase reflects the hormone-responsiveness of the intact tissue in m a n y aspects [10,11] it a p p e a r e d i m p r o b a b l e that stimulation of the human fat cell adenylate cyclase was a nonphysiological artifact. In this report evidence is presented which suggests that activation of the h u m a n fat cell adenylate cyclase by prostaglandins is related to the stimulatory c o m p o n e n t of prostaglandin action u p o n lipolysis.…”