Changes in plasma catecholamine levels after the intraperitoneal and intracerebroventricular administration of adenosine analogues and of clonidine in conscious rats.
When an adenosine analogue, N6-(amido-3-propyl) adenosine hydrochloride (Agr 529) is administered systemically, it causes a substantial release of epinephrine (E) by the adrenal medulla with no change in plasma norepinephrine (NE) levels. Low doses of N6-R-phenylisopropyl adenosine (L-PIA), an agonist of adenosine A1 receptors, has no significant effect on plasma epinephrine levels, which are increased by high doses of the analogue. Low doses of 5'-N-ethylcarboxamido-adenosine (NECA), an agonist of adenosine A2 receptors, however, lead to increases. The intracerebroventricular (icv) administration of Agr 529 leads to a significant decrease in plasma NE without affecting E levels. This action is synergistic with that of clonidine icv. The mechanism of central action of this effect is discussed. It can be admitted that the inhibitory effect of adenosine analogues icv occurs via an inhibition of the posterolateral hypothalamus and the locus coeruleus, although we cannot rule out an action on more rostral-situated brain regions. The authors suggest that the central effect of Agr 529 results primarily from the inhibition of central acetylcholine release caused by adenosine analogues and review experimental arguments enabling this hypothesis to be supported. On the other hand, the considerable release of plasma epinephrine seen when adenosine analogues are administered systemically can be attributed to their stimulation of ACTH secretion by the pituitary and the increase in glucocorticoids in the adrenal medulla, as a result of the existence of the cortico-medullary portal system. These glucocorticoids stimulate phenylethanolamine-N-methyltransferase, which transforms norepinephrine to epinephrine.
Laborit
H
H
Laboratoire d'Eutonologie, Hôpital Boucicaut, Paris, France.
Manzo-Fay
G
G
Baron
C
C
Hasni
H
H
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004837:Epinephrine / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects
D011983:Receptors, Purinergic; C065348:N(6)-(amido-3-propyl)adenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000241:Adenosine; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine