A thiol proteinase inhibitor, E-64-d, corrects the abnormalities in concanavalin A cap formation and the lysosomal enzyme activity in leucocytes from patients with Chediak-Higashi syndrome by reversing the down-regulated protein kinase C activity

ABSTRACT The effect of α-melanocyte-stimulating hormone (α-MSH) on protein kinase C activity and distribution was investigated in murine B16 F1 melanoma cells, α-MSH was found to induce an increased association of protein kinase C (PKC) activity with the particulate fraction of the cells, with an associated loss of enzyme activity from the soluble fraction. The peak response to α-MSH occurred between 20 and 60 min of incubation time, and enzyme activities redistributed to those seen in the control cells over the following 12 to 24 h. The average response to α-MSH (1 nmol/l) was an approximate 2·5-fold increase in the percentage of enzyme activity associated with the membrane within 1 h of exposure to α-MSH; the particulate enzyme activity represented 19·2 ± 4·4% of total activity in the absence of α-MSH and 50·7 ± 4·7% (means ± s.e.m., n = 9, P < 0·005) in the presence of α-MSH (1 nmol/l). Cells which had a relatively small percentage of their PKC activity on the membrane initially were significantly (P < 0·01) more responsive to α-MSH stimulation than cells which initially had a relatively large percentage of PKC activity on the membrane. The association of PKC activity with the membrane showed some evidence of being dose-related to α-MSH. This is the first report, to the best of our knowledge, of α-MSH activating PKC. Journal of Endocrinology (1992) 133, 333–340

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Chronic treatment by the calcium channel blocker ± PN 200-110 in the rat counteracts the stimulations of pituitary weight, prolactin release and pituitary C-kinase activity induced by a chronic estradiol treatment, in vivo

Acta Endocrinologica ◽

10.1530/acta.0.1220403 ◽

1990 ◽

Vol 122 (3) ◽

pp. 403-408

Author(s):

Ph. Touraine ◽

P. Birman ◽

F. Bai-Grenier ◽

C. Dubray ◽

F. Peillon ◽

...

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Calcium Channel ◽

Calcium Channel Blocker ◽

Channel Blocker ◽

Plasma Prolactin ◽

Estradiol Treatment ◽

Kinase C ◽

Protein Kinase C Activity

Abstract In order to investigate whether a calcium channel blocker could modulate the protein kinase C activity in normal and estradiol pretreated rat pituitary, female Wistar rats were treated or not (controls) with ± PN 200-110 (3 mg · kg−1 · day−1, sc) for 8 days or with estradiol cervical implants for 8 or 15 days, alone or in combination with PN 200-110 the last 8 days. Estradiol treatment induced a significant increase in plasma prolactin levels and pituitary weight. PN 200-110 administered to normal rats did not modify these parameters, whereas it reduced the effects of the 15 days estradiol treatment on prolactin levels (53.1 ± 4.9 vs 95.0 ±9.1 μg/l, p<0.0001) and pituitary weight (19.9 ± 0.4 vs 23.0 ± 0.6 mg, p <0.001), to values statistically comparable to those measured after 8 days of estradiol treatment. PN 200-110 alone did not induce any change in protein kinase C activity as compared with controls. In contrast, PN 200-110 treatment significantly counteracted the large increase in soluble activity and the decrease in the particulate one induced by estradiol between day 8 and day 15. We conclude that PN 200-110 opposed the stimulatory effects of chronic in vivo estradiol treatment on plasma prolactin levels and pituitary weight and that this regulation was related to a concomitant modulation of the protein kinase C activity.

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