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T Land

Publications and source records attributed to T Land.

29 records · Page 2Linked to original sources
PubMed1991

M-15: high-affinity chimeric peptide that blocks the neuronal actions of galanin in the hippocampus, locus coeruleus, and spinal cord.

The 20-amino acid peptide M-15 binds with high affinity (IC50 approximately 0.1 nM) to 125I-labeled galanin (125I-GAL) binding sites in membranes from the ventral hippocampus, midbrain, and rat spinal cord. Receptor autoradiographic studies show that M-15 can displace 125I-GAL from all labeled sites. M-15 acts as a reversible high-affinity antagonist in blocking the inhibitory effects of GAL on the evoked release of acetylcholine in vivo in the hippocampus and on the GAL-induced hyperpolarization of locus coeruleus neurons in slices. M-15 also blocks the facilitatory effects of GAL on the spinal flexor reflex. Thus, the chimeric peptide M-15 [GAL-(1-13)-substance P-(5-11)amide] represents the first antagonist to the neuronal actions of GAL.

Acetylcholine↗
PubMed1991

Hypothalamic degradation of galanin(1-29) and galanin(1-16): identification and characterization of the peptidolytic products.

The degradation of the neuropeptide galanin(1-29) and its fully active synthetic N-terminal fragment galanin(1-16) in hypothalamic tissue, where these peptides potently affect feeding behaviour, is studied. Galanin(1-29) had a half-life of 100 min while galanin(1-16) had a half-life of 28 min when incubated with a hypothalamic membrane preparation. The putative sites of peptidolytic cleavage of the active N-terminal fragment galanin(1-16) were determined as being between amino acids Leu4 and Asn5, between Asn5 and Ser6, and between His14 and Ala15, respectively. The synthetic analogs of galanin(1-16) where Leu4, Asn5 or Ser6 was substituted by Ala were all more stable to peptidolysis; [Ala4]galanin(1-16) had a half-life of 55 min. Cleavage of the galanin(1-16) between His14-Ala15 yields a ligand-galanin(1-14) which binds to the receptor with high affinity (KD approximately 10(7) M), while cleavage at amino acid residues Leu4, Asn5 and Ser6 results in inactive peptide fragments with affinities for the galanin receptor below 10(-4) M. The enzyme(s) responsible for degradation of galanin were identified as endopeptidase(s), which were partially inhibited by bacitracin (1 mg/ml) by up to 50%, but not significantly by EDTA (1 mM), phosphoramidon (1 microM), phenylmethylsulfonyl fluoride, (100 microM) or aprotinin (10 micrograms/ml).

Amino Acid Sequence↗
PubMed1991

Linear and cyclic N-terminal galanin fragments and analogs as ligands at the hypothalamic galanin receptor.

The neuropeptide galanin (1-29) binds with high affinity to hypothalamic receptors (KD approximately 0.9 nM) and regulates feeding behavior. The N-terminal fragments (1-16), (1-16)NH2 are high affinity (KD approximately 6 nM) full agonists in vivo and in vitro. L-Ala substitutions show that amino acid residues Gly1, Trp2, Asn5, Tyr9, and Gly12 are important for the high affinity binding of galanin (1-16). Shortening the fragment (1-16) to galanin (1-7) causes a gradual drop of affinity: galanin (1-15), (1-14), and (1-13) have submicromolar KD values and galanin (1-12) has KD approximately 3 microM. Cyclic analogs of galanin (1-12) of different ring size were synthesized by condensing Gly1 and Gly12 without or with spacer groups. These analogs, independent of ring size, had a lower affinity than the linear galanin (1-12). Derivatization of the N-terminus of galanin (1-29), (1-16), and (1-12) all resulted in a large drop of affinity for the receptors, suggesting again the importance of the free N-terminal Gly.

Alanine↗
PubMed1984

Anatomical study of the rabbit's corneal-VIth nerve reflex: connections between cornea, trigeminal sensory complex, and the abducens and accessory abducens nuclei.

The corneal-VIth nerve reflex of the rabbit, involving retraction of the eyeball by the retractor bulbi muscle and the correlated extension of the nictitating membrane, has been suggested to be mediated by retractor bulbi motoneurons in the accessory abducens-(ACC) nucleus but not by those in the abducens (ABD) nucleus, and to consist of both a fast, disynaptic, component and a slower component mediated by the reticular formation (RF). We, therefore, employed the anterograde and retrograde transport of horseradish peroxidase (HRP) to examine the neural connections between anatomical structures proposed to be involved in the afferent limb of the corneal VIth nerve reflex. The transganglionic transport of HRP from cornea indicated a primary projection to the ventral half of pars oralis of the trigeminal sensory complex. The retrograde transport of HRP infused into ACC resulted in a bilateral labeling of cells in ventral pars oralis with 75% of the labeled cells being ipsilateral to the side of infusion. In contrast, there was no retrograde labeling of cells in the trigeminal sensory complex after HRP infusions into ABD. Infusion of HRP into ACC and ABD also revealed retrogradely labeled cells in the RF caudal to these two nuclei and infusion of HRP into this area of the RF resulted in both the retrograde labeling of cells in ventral pars oralis and anterograde-like labeling in both ACC and ABD. These data provide anatomical support for a direct relationship of the ACC, but not ABD, to the trigeminal sensory system and for the suggested existence of two components of the corneal-VIth nerve reflex: a disynaptic component from cornea to ventral pars oralis which in turn projects only to the ACC nucleus; and a multisynaptic component consisting of projections from the ventral pars oralis to RF cells which, in turn, are premotor to the ACC and ABD nuclei.

Abducens Nerve↗
PubMed1980

Classical conditioning of the rabbit (Oryctolagus cuniculus) nictitating membrane response, with electrical brain stimulation as the unconditioned stimulus.

Rabbits were given classical conditioning training by using paired tone CS (conditioned stimulus) and brain-shock UCS (unconditioned stimulus), with the stimulating electrode localized in the vicinity of the abducens (6th nerve) nucleus such that the electrical stimulus elicited a low-threshold nictitating membrane (NM) extension response as the unconditioned response. Eight of the 27 animals developed clear conditioned NM responses to the tone CS. Control procedures, e.g., subsequent explicity unpaired training, argue against sensitization, pseudoconditioning, and "kindling" as possible explanations. There was no clear-cut anatomical differentiation of electrode-tip locations between learners and nonlearners. Both learners and nonlearners were subsequently trained with paired tone-corneal air puff, and neuronal unit activity was recorded from the stimulating electrode. Animals that had learned with the prior brain-shock UCS exhibited substantially greater increases in neuronal unit activity during air-puff training, which suggests the existence of a differentially effective anatomical-physiological substrate for conditionability.

Abducens Nerve↗
PubMedDate not supplied

Second-order conditioning of the rabbit's nictitating membrane response. Interstimulus interval and frequency of CS-CS pairings.

Second-order conditioning of the rabbit's nictitating membrane response (NMR) was investigated when second-order trials (CS1-CS2) were intermixed with first-order trials (CS2-US) from the outset of training. Experiment 1 showed that CR acquisition to CS1 was inversely related to the CS1-CS2 interval but nevertheless extended to an interval of 8,400 ms. Experiment 2 revealed that CR acquisition of CS1 was an inverted-U function of the number of CS1-CS2 trials relative to a fixed number of CS2-US trials. Experiment 3 directly contrasted second-order conditioning with a reinforced serial compound procedure (CS1-CS2-US) and a mixed procedure in which second-order trials were intermixed with the reinforced serial compound. Second-order conditioning was about half the strength of either the reinforced serial compound or the mixed procedure, which were similar. The present results are discussed with respect to the relative strength of excitatory and inhibitory processes in second-order conditioning.

Animals↗