Effect of diadenosine polyphosphates on catecholamine secretion from isolated chromaffin cells

Abstract

1 The action of several diadenosine polyphosphates (AP3A, AP4A and AP5A) on basal, and on nicotineand high K+-evoked, catecholamine (CA) release has been investigated. Each of the three diadenosine polyphosphates weakly but significantly increased basal CA secretion. This enhancement represented about 10% of the response evoked by 2 J1M nicotine. 2 The evoked secretory response to diadenosine polyphosphates had an absolute requirement for extracellular Ca2".3 In contrast, these compounds had an inhibitory action on nicotine-evoked release. This response was concentration-dependent, EC50 values being 3.2 + 0.4OAM, 4.0 + 1.6./M and 19.3 + 4.0/AM for AP A AP4A, and AP5A, respectively. The lower the concentration of nicotine used to evoke secretion, the higher the inhibitory power of these compounds.4 The CA secretion evoked by K+-rich solutions was further enhanced by AP3A and APA, whereas AP4A inhibited it. The possible physiological role of these dual actions is discussed.

A reassessment of the modulatory role of cyclic AMP in catecholamine secretion by chromaffin cells

“…Some of the previous studies on the effect of cyclic AMP on CA secretion in adrenal medulla have failed to demonstrate any significant effect on basal secretion (Morita et al, 1987;Chern et al, 1988;Marriot et al, 1988;Morita et al, 1991a), although others have demonstrated a significant increase in basal CA secretion by 1 tLM forskolin (Bader et al, 1989;Sontag et al, 1991), cyclic AMP (Bittner et al, 1986;Morgan et at., 1993) or by cyclic AMP-elevating agonists such as VIP (Wilson, 1988), adenylate cyclase activating polypeptide (PACAP) (Isobe et al, 1993) or adenosine (Castro et al, 1990).…”

Analogues of diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) as potential anti-platelet-aggregation agents.

“…More recently it has been recognized that Ap4A and its analogues play an important role in extracellular signaling events as well as in specific enzyme inhibition (7,(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). These extracellular functions draw attention to the possible role of Ap4A and its analogues as pharmacologically active compounds in cardiovascular, neurotransmitter, stress-related, and diverse purinergic fields.…”

Selectivity and activity of adenine dinucleotides at recombinant P2x2 and P2Y1 purinoceptors

“…lonotropic and metabotropic ATP receptors have been cloned from neural tissues, including a P2X2 purinoceptor from rat phaeochromatocytoma PC12 cells (Brake et al, 1994) and a P2Y, purinoceptor from embryonic chick brain (Webb et al, 1993). These particular recombinant P2 purinoceptors are distinguished by possessing pharmacological profiles similar to neuronal P2, and P2Y purinoceptors native to their source tissues (Simon et (Stone & Perkins, 1981;Castro et al, 1990;Klishin et al, 1994), we decided to investigate the actions of the full family of adenine dinucleotides (ApXA, x = 2-6) on these two recombinant P2 purinoceptor subtypes. Recently, it was reported that Ap4A is a potent agonist of the recombinant human P2y2 purinoceptor from non-neural (epithelial) tissue (Lazarowski et al, 1995) and, therefore, we were also interested to compare this earlier study with agonist actions of adenine dinucleotides at neurally-derived P2x2 and P2Y, subtypes of recombinant P2 purinoceptors.…”