Mechanism of the inhibition of catecholamine secretion by co-hormones in the adrenal medulla

Q8

9th Meeting of the ESN

MECHANSW INVOWED IN DOPAMINE D-2 AND RECEPTOR NEDWED REGUlATlON DF ACRELEASE FRDM SlRlAlUM

PRR!ruRRIS TOXIN BoB(ITRATRR UliD PRRSIRAPTIC RBQuLATIm OI ACRTYLCROLIRR IiRDRORADRRRALfRRRRLRASR IWRRAIR.

J.C. Stoof and B. Drukarch. Dept. Neurology, Med. Faculty, Free University, vd Boechorststr. 7, 1081 BT Amsterdam, The Netherlands

C. Allgaier and G. Hertting Department of Pharmacology and Toxicology, Albert-Ludwig6 University, Freiburg, Germany

Acetylcholine (ACh) release in rat striatum is regulated by D-2 receptors as well as muscarinic autoreceptors. In the present study, we collected evidence for the coupling of D-2 receptors, mediating the inhibition of ACh release from rat striil tissue, to K’channels as well as to Ca”-mobilizaton. Both transduction mechanisms operate independent from CAMP formation. Concerning homologous receptor regulation, we found that sustained activation of the D2 receptor did not lead to any desensitization of this receptor. Concerning heterologous receptor regulation, we found that stimulation of the muscarinic autoreceptor considerably attenuated the effect on ACh release upon stimulation of the D-2 receptor and vice versa. This phenomenon could be explained by the finding that also the muscarinic autoreceptor exerts its inhibitory control of ACh release to a large extent through the opening of K’channels. lt was concluded that the interaction between the two receptor types occurs through competition for the same pool of “signaltransduction molecules”.

Electrically evoked release of [3H]acetylcholine and [3H]noradrenaline in rabbit hfppooampua is inhibited by activation of the respective autoreceptors (muacarine receptors, 02-adrenoceptors) and adenoaine A1 and opioid k receptors. Noradrenergic nerve endings in rat cortex are equipped in addition with inhibitory PGE receptors. Three preaynaptically located Pertussis toxin (PTX)-sensitive G proteins, which were also targets for the SH-reagent N-ethylmaleimide (NE&I) were identified in brain tissue. Inhibition of transmitter release caused by oxotremorine, clonidine, RPIA, ethylketocyclazocine (H, c2-, adenosine, opioid receptor agonists, respectively) was markedly diminished following treatment of the slices with either PTX or NEH indicating that these presynaptic receptors couple to PTX-sensitive G proteins. In contrast the effect of PGEX was not influenced by these compounds.

THE IRRIBITION OF BBCRRTION BY COIN THE ADRENAL MEDULLA OF

DIRECT ACTIVATION BY ALF - OF a-SUBUNIT OF G-PROTEINS RELEASES bOPAMINE IN A [CA2+],-INDEPENDENT WAY

HECRARISX

Vii, E.S., Chemaeva, L., Zelles, T. and Baranyi, M. Institute of BxperimentaI Medicine, Hungarian Academy of Sciences, H1450 Budapest, PGBox 67, Hungary.

P. Illea, M. Bek and W. NiSrenberg Department of Pharmacology, University of

The effect of AlQ~complex, a direct activator of u-subunit of Gproteins, on the release of [3H]-dopamine @HIDA), was studied in slices of rat striatum. In the tissues preloaded with [3H]DA resting release in 3 mm was l.l+O.l2 % of radioactive content of the tissue and electriwI stimulation (2 Hz, 240 shocks) resulted in a Ifold increase in the release. When the tissue was exposed to AlF4- for 30 min the basal release of [3H]DA was enhanced 2.81 f 0.56(5) times. In calcium-free sohnioninthe presence of1 mMEGTAther&ase of[3HjDA

Stimulation of bovine adrenal chromaffin cells releases a mixture of catecholaminea. A number of co-hormones, such as adenosine 5'-triphosphate (ATP) and neuropeptide Y (NPY) are also secreted. Of the catecholaminea, only dopamine modulates the release

CATECNOLAHINA

HORRORES

Freiburg,

Freiburg

i.Br., Germany

and the underlying ionic conductancea both While Dl-agonists at Dl- and Dg-receptors. voltage-dependent calcium the inrfqnmsctoALF4~wssmuch higher thaninthe presence of facilitate incurrent (ICa), the Dz-agonist quinpirol [Ca*+],. On slice preparation t&n hornrescrpinized animals The nicotinic current (IACh) is AlF4- had no effecton [3HJDA relcasc, i.e. undercondition hibits it. also depressed by Dg-receptor activation. tien the vesicular storage of[3HjDAwssprevented Neomycin Although the a2-adrenoceptor agonist cloni(0.1 mM), a phospholipase C inhiitor, signiticantly decreased and adrenadine blocks IACh, noradrenaline the effect of Al&- on r31-BDA release suggesting that a-subunit stuline are inactive. Of the co-hormones of G-protein coupled to phospholipase C may be, at least partly, died, ATP inhibits ICa in moat cells; in a responsible for the Ca-independent release. Pertussis toxin few cells ICa is facilitated by the purine. (PTX) in viva pretreatment and N-ethyhnaleimide (NBM) NPY depresses l&Gh, but does not alter IGa. preincubation did not affect the effect of AlF4-complexon

In conclusion, clonidine and guinpirol cause [3H]DAre1casc.ItisconchtdcdthatanactivationhyALF4~ofaan open-channel block of lAGh. NPY aCta at subunit of G-protein coupled to phospholipase C results in a an Y3-type receptor; it appears to inhibit release ofDAstoredinvasicleina[Ca*+]o-independentwsy. G-protein via a IACh adenylcyclase/proteinkinase

coupled to A system.

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