Neuroscience
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Angiotensin II (250 pmol) infused into the cerebral ventricles of male rats induces the expression of c-fos in the subfornical organ, supraoptic and paraventricular nuclei of the hypothalamus, as well as in the lateral parabrachial nucleus, locus coeruleus and the nucleus of the solitary tract in the brainstem. Electrolytic lesions of the anteroventral third ventricle, principally the subcommissural (ventral) median preoptic nucleus, inhibited the dipsogenic response to i.c.v. angiotensin II and also suppressed c-fos expression in supraoptic nucleus, paraventricular nucleus, lateral parabrachial nucleus, locus coeruleus and nucleus of the solitary tract but not in the subfornical organ or dorsal median preoptic nucleus. The stimulating effect of i.c.v. angiotensin II on corticosterone was also reduced. ⋯ These experiments show that the ventral median preoptic nucleus (but not the subfornical organ), part of the anteroventral third ventricle, is critical for the expression of c-fos in more caudal areas of the brain following i.c.v. angiotensin II. c-fos expression in supraoptic nucleus and paraventricular nucleus following i.v. angiotensin II is also dependent on an intact median preoptic nucleus, suggesting that supraoptic nucleus and paraventricular nucleus activation may be dependent on the median preoptic nucleus, and that suppression following i.c.v. infusions is not due to mechanical obstruction to infused peptide. However, there is a clear separation of the effects of i.c.v. and i.v. angiotensin II on brainstem structures. The median preoptic nucleus (but not the subfornical organ) seems essential for activation following the former but not the latter, suggesting alternative mechanisms for the effect of i.v. angiotension II on the brainstem.(ABSTRACT TRUNCATED AT 400 WORDS)
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Guanine nucleotide-binding regulatory protein stimulation of adenylyl cyclase has been shown to be an important second messenger system for many processes, including mechanical hyperalgesia. Recently, interactions between guanine nucleotide-binding regulatory protein subunits and adenylyl cyclase affecting the level of cyclic adenosine 3',5'-monophosphate accumulation have been demonstrated. In this study we evaluated such an interaction by measuring paw-withdrawal thresholds to mechanical stimuli in Sprague-Dawley rats in the presence of two direct-acting hyperalgesic agents, prostaglandin E2 and the adenosine A2-agonist, CGS21680. ⋯ On the other hand, injection of [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin 5 min after prostaglandin E2 or CGS21680 significantly enhanced the hyperalgesia observed. Injection of the adenosine A1-agonist N6-cyclopentyladenosine immediately before and 5 min after prostaglandin E2 or CGS21680 had a similar effect to [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin. The decrease in sensitivity to prostaglandin E2- and CGS21680-induced hyperalgesia by preadministration of [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin or N6-cyclopentyladenosine and the enhancement by postadministration were all reversed by pertussis toxin, an inhibitor of inhibitory guanine nucleotide-binding regulatory protein, suggesting the involvement of an inhibitory guanine nucleotide-binding regulatory protein.(ABSTRACT TRUNCATED AT 250 WORDS)