Angiotensin receptor in the heart of Bothrops jararaca snake.

Angiotensin II interacts with specific cell surface angiotensin AT1 and AT2 receptors and, in some vertebrates, with an atypical angiotensin AT receptor. This study was designed to characterize the angiotensin receptor in the heart of Bothrops jararaca snake. A specific and saturable angiotensin II binding site was detected in cardiac membranes and yielded Kd=7.34+/-1.41 nM and B(max)=72.49+/-18 fmol/mg protein. Competition-binding studies showed an angiotensin receptor with low affinity to both angiotensin receptor antagonists, losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole) and PD123319 ((s)-1-(4-[dimethylamino]-3-methylphenyl)methyl-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylate). Studies on the intracellular signaling pathways showed that phospholipase C/inositol phosphate breakdown and adenylylcyclase/cyclic AMP generation were not coupled with this angiotensin receptor. An adenylylcyclase enzyme sensitive to forskolin was detected. The results indicate the presence of an angiotensin receptor in the heart of B. jararaca snake pharmacologically distinct from angiotensin AT1 and AT2 receptors. It seems to belong to a new class of angiotensin receptors, like some other atypical angiotensin AT receptors that have already been described.

Atypical angiotensin receptors may mediate water intake induced by central injections of angiotensin II and of serotonin in pigeons.

Intracerebroventricular (i.c.v.) injection of serotonin (5-HT) in pigeons dose-dependently evokes a prompt and intense drinking behavior, which resembles that evoked by i.c.v. injections of angiotensin II (ANGII) in the same species. In the present study, we have examined the possible participation of central ANGII receptors in both ANGII- and 5-HT-evoked drinking behavior. The effects of i.c.v. injections of 5-HT (155 nmol), avian ANGII ([Asp(1),Val(5)]-ANGII, 0.1 nmol) or vehicle were studied in pigeons pretreated 20 min before with i.c.v. injections of the nonspecific ANGII receptor antagonist [Sar(1),Ile(8)]-ANGII (SAR; 1, 0.1 or 0.01 nmol), the AT(1) receptor antagonist losartan (2 or 4 nmol), the AT(2) receptor antagonist PD 123,319 (2 or 4 nmol) or vehicle (NaCl 0.15 M, 1 microl, n = 8/group). Immediately after treatment, they were given free access to water and drinking behavior was recorded during the next 60 min. At the doses presently used both 5-HT and ANGII treatments evoked comparable water intake amounts with similar behavioral profiles. While pretreatment with SAR dose-dependently reduced the water intake evoked by both 5-HT and ANGII, neither losartan nor PD 123,319 pretreatment affected the drinking induced by these treatments. The present results indicate that ANGII- and 5-HT-induced drinking in pigeons may be mediated by AT receptors possibly different from mammalian AT(1) and AT(2) receptors and suggest that activation of ANGII central circuits is a necessary step for the intense drinking induced by i.c.v. injections of 5-HT in this species.

Effect of intravenous captopril on c-fos expression induced by sodium depletion in neurons of the lamina terminalis.

Peripheral administration of the angiotensin converting enzyme (ACE) inhibitor, captopril, and the central infusion of sarile, an angiotensin II (Ang II) receptor antagonist, were used to evaluate the role of renal and brain generated Ang II in sodium depletion-induced production of Fos in cells of the subfornical organ (SFO) and organum vasculosum lamina terminalis (OVLT). Pretreatment with intravenous captopril (100 mg/kg) significantly inhibited the c-fos expression induced by sodium depletion in the SFO and OVLT. In contrast, continuous intracerebroventricular infusion of sarile (22.5 micrograms/4.5 h, 5 microliters/h) did not affect the expected pattern of c-fos expression observed in both nuclei, 4 h after peritoneal dialysis. These results show that systemic interference with the angiotensin system of renal origin by captopril inhibited the production of Fos induced by sodium depletion in cells of the SFO and OVLT. These findings are consistent with the hypothesis that a rise in peripheral Ang II levels, triggered by sodium deficiency, could be an important mediator of the physiological and behavioral responses that lead to the restoration of sodium balance. In addition, this study suggests that increased circulating Ang II levels in response to body sodium deficit can directly stimulate neural pathways in the SFO and OVLT.

Interaction of angiotensin II with the cholinergic and noradrenergic systems in the rat pineal gland: regulation of indole metabolism.

The pineal gland, angiotensin, and noradrenergic and cholinergic systems are involved in the regulation of tissue indole metabolism. Angiotensin II increased noradrenaline release and the production of hydroxy- and methoxyindoles by pineal slices. Electrical field stimulation (EFS) of pineal slices released angiotensin II and reproduced many of the actions of exogenous angiotensin II on serotonin and melatonin biosynthesis and release. Both sarcosine-isoleucine-angiotensin II ([Sar, Ile]-ANG II) and atropine blocked, and nadolol increased, the effect of EFS and exogenous angiotensin II on serotonin production. Nadolol blocked both the EFS-induced and the angiotensin II-induced production of melatonin. Atropine and [Sar, Ile]-ANG II did not modify melatonin biosynthesis in electrically stimulated slices, but the muscarinic receptor antagonist increased the stimulatory effect of angiotensin II. These data showed that EFS released angiotensin II and noradrenaline from pineal slices and that a close functional connection exists between the peptide and acetylcholine. The stimulation of serotonin biosynthesis and release by these two neurotransmitters was negatively regulated by noradrenaline acting through beta-adrenergic receptors.