Page 10 - 71_02

GEOFFREY BURNSTOCK AN. R. ACAD. NAC. FARM.

It has been proposed that there is prognostic value of stress
myocardial perfusion imaging using ATP at the beginning of
haemodialysis treatment in patients with end-stage renal disease.

DERMATOLOGY

Purinergic signalling is much involved in keratinocyte turnover
in skin epidermis: P2Y1 and P2Y2 receptors in basal and parabasal
layers mediate cell proliferation; P2X receptors in the granular layer
mediate cell differentiation; and P2X7 receptors at the stratum
granulosum/stratum corneum border mediate apoptosis (8). There
are changes in the expression of P2 receptors in proliferative
disorders of the epidermis, including psoriasis and scleroderma and
P2Y2 receptors have been proposed as a novel target for therapy of
these disorders.

There is an increase of P2X3 and P2X2/3 nociceptive receptors on
sensory nerve endings in inflamed skin and antagonists are being
developed as analgesics (see section on Pain); data have been
presented to support a pathogenic role for keratinocyte-derived ATP
in irritant dermatitis.

Changes in expression of purinergic receptors in the regenerating
epidermis in wound healing have been described. The P2X
receptor antagonist, PPADS, has been shown to accelerate skin barrier
repair and prevent epidermal hyperplasia induced by skin
barrier disruption.

Purinergic signalling involved in skin tumours is discussed
in the section on Oncology.

DIABETES

Early studies from the laboratory of Loubatières-Mariani showed
that P2Y receptors are present on pancreatic b-cells and are involved
in insulin secretion. ATP stimulates pancreatic insulin release
through a glucose-dependent P2Y receptor-mediated mechanism,
and also modulates insulin secretion through interactions with

290