Damage to the nucleus accumbens shell but not core impairs ventral tegmental area stimulation-induced feeding.

Food intake is regulated not only by homeostatic requirements but also by emotional factors (e.g. palatability of food, alleviation of emotional tension etc.). The nucleus accumbens (Acb) is a part of the mesolimbic dopaminergic system which is responsible for a positive emotional aspect of various homeostasis-relevant stimuli. In the present work, we tested the Acb involvement in feeding behaviour using an experimental paradigm specifically designed to assess motivational vs motor aspect of food ingestion. In rats, feeding was evoked by electrical stimulation of the midbrain ventral tegmental area (a somatodendritic region of mesolimbic system) and assessed quantitatively with the use of the latency to feed/stimulation frequency curve-shift paradigm before and after electrolytic lesion of Acb. An impairment of stimulation-induced feeding manifesting as an elevation of the reaction threshold and a rightward, parallel shift of the stimulation frequency/reaction latency curve in the range of frequency which is sensitive to motivational aspects of food occurred after lesions localized mainly in the Acb shell. The lesions situated mainly in the Acb core were ineffective. The results obtained indicate that the Acb shell connected with the limbic system but not the motor-related Acb core affects motivational aspects of feeding behaviour.

Synthesis of angiotensin II analogues by incorporating beta-homotyrosine or beta-homoisoleucine residues.

[1-Sarcosine,4-beta-homotyrosine]-(I), [5-beta-homoisoleucine]-(II), and [1-sarcosine,5-beta-homoisoleucine]angiotensin II (III) were synthesized by Merrifield's solid-phase procedure to study the effect of pressor activity and duration of action. The analogues I--III possessed, respectively, 1.98, 2.82, and 29.2% pressor activity of angiotensin II (vagotomized, ganglion-blocked rats by single-injection procedure) and duration of action of 5.5, 6.7, and 4.7 min; the comparative duration of action of an equipressor dose of angiotensin II was 5.2, 6.3, and 5.3 min, respectively. When incubated with leucine aminopeptidase, degradation of II was as fast as that of angiotensin II; this degradation became considerably slower when position 1 was replaced with sarcosine. Incubation of all these analogues with chymotrypsin showed very little or no degradation up to 3 h. The results indicate that an increase in the chain length by one carbon atom in position 4 or 5 of angiotensin II increased resistance to degradation by chymotrypsin without any increase in in vivo duration of action. Further, all analogues showed low pressor activity.

Multiple binding modes for the receptor-bound conformations of cyclic AII agonists.

Angiotensin II, Asp-Arg-Val-Tyr-His-Pro-Phe, binds its receptor with a postulated turn centered at residue four. Analogs of angiotensin II which contain a disulfide bridge between the side chains of residues 3 and 5 retain significant activity consistent with this hypothesis. Incorporation of 4-mercaptoproline residues, a hybrid, or chimeric amino acid which combines the properties of proline and homocysteine, into either of these positions with analogous disulfide bridges allows retention of high affinity for the receptor. These more highly constrained bicyclic systems give new insight into the details of molecular recognition of residues 3-5 of angiotensin by the receptor. Retention of activity by the antiparallel dimer of [Sar1,Cys3,5]-AII in which the peptide backbone is held in an extended conformation was unexpected. Analysis of the conformational constraints imposed in these active analogs suggests that AII agonists bind to their receptor with different backbone conformations in the region of the central tyrosine residue.

[Induced abortion in the second trimester by intra-amniotic administration of PGF2 alpha]. / Przerwanie ciazy w II trymestrze przy pomocy doowodniowego podawania prostaglandyny F2 alfa.

PIP: A group of 15 women between the ages of 24-45 were given intraamiotic does of 40 mg of prostagladin F2alpha (PGF2alpha; Enzaprost) in a single dose so as to terminate pregnancy. These pregnancies, between the 15th- 24th weeks, were terminated for medical reasons. 12 hours elapsed between the time of intraamniotic administration and the appearance of labor pains, with the average being 9 hours. Labor lasted between 3-19 hours, with the average being 9 hours. The authors found that the time which lapsed between PG administration and the onset of labor was longer among multiparas but the length of labor was extended in primigravidae; the difference was not statistically different. The procedure was considered successful in all cases as there was no need to use other methods. Complications were not observed and there were no side effects connected with the intravenous administration of the PGs. (author's modified)^ieng

Conformational analysis of two cyclic analogs of angiotensin: implications for the biologically active conformation.

Conformations of two cyclic analogs of angiotensin (Asp1-Arg2-Val3-Tyr4-Val/Ile5-His6-Pro7-Phe8, AT), cyclo[Sar1, Cys3, Mpt5]-AT and cyclo[Sar1, HCys3, Mpt5]-AT, were studied, independently employing two complementary techniques, energy calculations and NMR measurements in DMSO solution. NMR data were indicative of well-defined solution conformations for the cyclic moieties of cyclo[Sar1, Cys3, Mpt5]-AT and cyclo[Sar1, HCys3, Mpt5]-AT, including the phi values for the Cys3/HCys3 and Tyr4 residues, as well as the chi 1 value for the Tyr4 residue. Solution conformations for the exocyclic linear parts of both molecules cannot be described by the NMR data with the same precision. At the same time, independent energy calculations revealed the same conformations of cyclic moieties of cyclo[Sar1, Cys3, Mpt5]-AT and cyclo[Sar1, HCys3, Mpt5]-AT among low-energy conformers for both peptides. Moreover, the same conformations are compatible with the model of AT receptor-bound conformation (Nikiforovich & Marshall, 1993), which assumes the particular spatial arrangement of aromatic moieties of Tyr4, His6, and Phe8 residues and the C-terminal carboxyl. These conformers of cyclo[Sar1, Cys3, Mpt5]-AT and cyclo[Sar1, HCys3, Mpt5]-AT contain "an open turn" in the backbone of the Tyr4-Val5 residues, instead of the earlier proposed beta-like reversal, thus confirming the suggestion that the conformation(s) ensuring binding of AT analogs with specific receptors should not be described in terms of a unique backbone conformer.