Allosteric-type control of synaptobrevin cleavage by protect tetanus toxin light chain

The light chain of tetanus neurotoxin (TeNT L chain)has been shown to be endowed with zinc endopeptidaseactivity, selectively directed towards theGln⁷⁶–Phe⁷⁷ bond of synaptobrevin, avesicle-associated membrane protein criticallyinvolved in neuroexocytosis. In previous reports,truncations at the NH₂- and COOH-terminus ofsynaptobrevin have shown that the sequence 39–88 ofsynaptobrevin is the minimum substrate of TeNT,suggesting either the requirement of a well-definedthree-dimensional structure of synaptobrevin or a rolein the mechanism of substrate hydrolysis for residuesdistal from the cleavage site. In this study, theaddition of NH₂- and COOH-terminal peptides ofsynaptobrevin, S 27–55 (S₁) and S 82–93(S₂), to the synaptobrevin fragment S 56–81allowed the cleavage of this latter peptide by TeNT tooccur. This appears to result from an activationprocess mediated by the simultaneous binding ofS₁ and S₂ with complementary sites presenton TeNT as shown by surface plasmon resonanceexperiments. All these results favor anexosite-controlled hydrolysis of synaptobrevin by TeNTprobably involving a conformational change of thetoxin. This could account for the high degree ofsubstrate specificity of TeNT and, probably, botulinumneurotoxins.     

Attack and defensive behaviour in the albino rat

Attack of dominant colony males of an albino rat (Rattus norvegicus) strain, on introduced strangers, produced a non-random distribution of bites, with ventral trunk virtually never bitten. Also, vibrissae-contact of attacker and defender interfered with bites to the defender's head and upper back. The specific agonistic reactions of attacking and defending rats appeared to involve strategies based on these limitation on attack: defenders utilized 'boxing' and lying 'on-the-back' behaviour, which interposed ventral trunk and vibrissae between attacker and defender. In turn, the 'lateral display' permitted attackers to circumvent the defender's behaviour. Limitations on attack therefore appeared to underlie the specific agonistic behaviour of both attacking and defending rats.     

Studies on the mechanism of enkephalin receptor down regulation

The association of [3H] [D-Ala2, D-Leu5] enkephalin ([3H]DADLE]) with mouse neuroblastoma cells (N4TG1) was investigated. Under identical conditions the time course, dose response curve and temperature dependence for ligand uptake were similar to those for ligand-induced receptor loss (down regulation). Uptake of [3H]DADLE was inhibited by opiate ligands as well as by the metabolic inhibitors sodium azide and 2,4 dinitrophenol. Comparison of the effects of these inhibitors on receptor binding, ligand uptake and receptor loss indicated that these cells accumulate [3H]DADLE in excess of their surface receptor number. The data suggest that receptor recycling occurs and that ligand is internalized via receptor mediated endocytosis.     

Preliminary results from the self-regulatory treatment of high-medication-consumption headache

Data are presented from a prospective clinical replication series of ten consecutive high-medication headache patients who presented for nondrug treatment of their headaches. For the first eight, an attempt was made to withdraw the patients from medication, with the assistance of relaxation training, prior to entering a comprehensive self-regulatory treatment program. For the last two, drug withdrawal accompanied the treatment. Six of the ten patients showed clinically significant reductions in headache activity, which held up over follow-ups of up to 12 months. Psychological tests provide some discrimination between success and failures.This research was supported in part by a grant from NINDS, No. NS-23340. Appreciation is expressed to Dr. Kenneth A. Appelbaum and Ms. Denise Michultka for their roles in this study.     

The treatment of cluster headache with relaxation and thermal biofeedback

Eleven patients with episodic cluster headache were assessed and offered a treatment program consisting of 8 weeks of training in abbreviated progressive relaxation followed by 12 sessions of thermal biofeedback. Four dropped out before treatment began. Of the seven who completed the full treatment regimen, three (27% of initial sample) reported some degree of improvement when their next cluster bout occurred. In no one was the disorder eliminated.This research was supported by a grant from the National Institute of Neurological and Communicative Disorders and Stroke, NS-15235.