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Biomedical subjects

S C Robertson

Publications and source records attributed to S C Robertson.

6 recordsLinked to original sources

Crystal structure of the phosphotyrosine recognition domain SH2 of v-src complexed with tyrosine-phosphorylated peptides.

Three-dimensional structures of complexes of the SH2 domain of the v-src oncogene product with two phosphotyrosyl peptides have been determined by X-ray crystallography at resolutions of 1.5 and 2.0 A, respectively. A central antiparallel beta-sheet in the structure is flanked by two alpha-helices, with peptide binding mediated by the sheet, intervening loops and one of the helices. The specific recognition of phosphotyrosine involves amino-aromatic interactions between lysine and arginine side chains and the ring system in addition to hydrogen-bonding interactions with the phosphate.

Amino Acid Sequence

Mechanisms of cardiovascular responses to glycine injected into the dorsal vagal motor nucleus in rat.

Microinjection of glycine into the dorsal vagal motor nucleus of anesthetized rats elicits increases in arterial pressure and heart rate. In the nucleus tractus solitarii, where cardiovascular responses to injection of glycine may be mediated through release of acetylcholine, there is a dense concentration of glycinergic nerve terminals and glycine receptors. In this study, using immunohistochemical methods, we show that glycine terminals and receptors are present in caudal dorsal vagal motor nucleus, although the concentration of both terminal elements is less than in adjacent nucleus tractus solitarii. Responses to glycine microinjected into the dorsal vagal motor nucleus are blocked by the muscarinic antagonist atropine microinjected at the same site; but, unlike responses to glycine in the nucleus tractus solitarii, responses to glycine in the dorsal vagal motor nucleus are not prolonged by physostigmine. These data support the possibility that endogenous glycine may play a role as a transmitter in the dorsal vagal motor nucleus. Responses to glycine may be mediated through actions at muscarinic receptors but not through acetylcholine itself.

Animals

Glycine microinjected into nucleus tractus solitarii of rat acts through cholinergic mechanisms.

Previous studies have demonstrated the release of glycine from neurotransmitter pools in the region of the nucleus tractus solitarii (NTS) where cardiovascular afferents terminate. Microinjection of glycine into NTS elicits decreases in arterial pressure and heart rate; these effects are also produced by glutamate or acetylcholine. As glycine may act both at the N-methyl-D-aspartate (NMDA)-receptor complex and centrally to release acetylcholine, we have sought to determine whether the cardiovascular responses to exogenous glycine are mediated through glutamatergic or cholinergic mechanisms. Responses to glycine microinjected into the NTS of anesthetized rats were not affected by blockade of the NMDA receptor complex but, like acetylcholine, were blocked by muscarinic receptor blockade. Physostigmine prolonged responses to glycine. Subthreshold doses of glycine, which augmented responses to acetylcholine microinjected into NTS, either decreased or had no effect on glutamate or NMDA. This study supports a role for glycine in cardiovascular regulation by the NTS and suggests that the actions of glycine may be effected, at least in part, through cholinergic mechanisms.

Acetylcholine

Nucleus prepositus hypoglossi. A medullary pressor region.

Electrical stimulation of fibers of passage through the fastigial nucleus increases arterial pressure. To identify nuclei that may project through the pressor region of the fastigial nucleus, we injected the retrograde tracer fast blue unilaterally at confirmed pressor sites in the nucleus. In seven rats, we found dense fluorescent labeling bilaterally in the external cuneate, lateral reticular, medial vestibular, and caudal prepositus hypoglossi nuclei, and contralaterally in the inferior olivary nucleus. There had been no reports of a cardiovascular role for the nucleus prepositus hypoglossi; thus, we sought to determine if electrical or chemical stimulation of that nucleus or the adjacent medial vestibular nucleus altered arterial pressure or heart rate in 24 anesthetized rats. Both types of stimuli to the caudal, but not the rostral, pole of the nucleus prepositus hypoglossi or to the medial vestibular nucleus elicited an increase in arterial pressure; bradycardia accompanied the former and tachycardia the latter. Both the nucleus prepositus hypoglossi and medial vestibular nucleus may participate in central cardiovascular regulation.

Animals

Glycine, like glutamate, microinjected into the nucleus tractus solitarii of rat decreases arterial pressure and heart rate.

Glycinergic mechanisms have been implicated in central cardiovascular regulation. However, the inhibitory amino acid's role in the nucleus tractus solitarii (NTS), the site of termination of cardiovascular afferents, has not been clarified. Thus, we sought to determine if the microinjection of glycine into the NTS alters arterial pressure and heart rate. Microinjections of glycine, like glutamate, confined to the NTS decreased arterial pressure and heart rate in a neurally mediated, dose-dependent manner. The glycine antagonist strychnine completely blocked these effects of glycine but did not itself alter arterial pressure or heart rate, or interfere with the baroreceptor reflex. The acute hypotensive, bradycardic response to glycine was followed by a period during which glycine essentially eliminated the cardiovascular responses to the microinjection into the NTS of glutamate, an amino acid reputed to be a transmitter in the baroreceptor reflex arc. These data suggest that glycine is involved in cardiovascular regulation by the NTS but do not support its being an integral transmitter in the baroreceptor reflex.

Animals