No abstract

1. On unilateral injection of sublethal doses of 125I-botulinum A neurotoxin (BTA) into one gastrocnemius muscle of the cat we found after 48 h: a) A disto-proximal gradient of radioactivity (RA) had developed in the sciatic nerve of the injected side. b) The ventral roots of the spinal cord half segments supplying the injected muscle showed a higher RA than the ventral roots of the contralateral control side. c) The spinal cord half segments innervating the injected muscle had a RA much higher than the corresponding segments of the contralateral side. However, a small rise of RA was also observed in the contralateral half segments. 2. In histoautoradiographs of the (ligatured) ventral roots the RA was strictly confined to the intraaxonal space of a few nerve fibres. 3. On injection of equal doses of 125I-BTA into either gastrocnemius muscle we found after 38 h: a) Direct stimulation of only one of the injected muscle caused the RA to reach a higher level in the spinal cord half segments ipsilateral to the stimulated muscle than in the spinal cord half segments of the non-stimulated side. b) Unilateral stimulation of one gastrocnemius nerve under the influence of gallamine or unilateral antidromic stimulation of the dorsal roots L7, S1 failed to cause a difference in RA between stimulated and non-stimulated side.

PF1022A belongs to a new class of cyclodepsipeptides with broad anthelmintic activity. Here, we describe a novel target for PF1022A. Using PF1022A ligand immunoscreening of a cDNA library constructed from the parasitic nematode Haemonchus contortus, we identified a 3539 bp cDNA encoding a novel orphan heptahelical transmembrane 110 kDa‐receptor, termed HC110‐ R, similar to the mammalian G‐protein coupled receptor latrophilin. HC110‐R is localized at plasma membranes and in intracellular vesicles of HC110‐R‐transfected HEK‐293 cells. The ligand of latrophilin, a‐latrotoxin (LTX), binds to the extracellular N‐terminal region of HC110‐ R and induces influx of external Ca2+ through Cd2+‐ and nifedipine‐blockable Ca2+ channels. PF1022A also binds to the N‐terminus of HC110‐R and acts as an antagonist to LTX signaling in HC110‐R transfected HEK‐293 cells.

1. The central action of botulinum toxin A (BTA) on the cholinergic transmission at Renshaw cells (RCs) and on the RC-induced inhibition of Ia inhibitory interneurones (IaINs) was studied in anaesthetized cats. BTA was administered by application directly into the spinal cord, injection into a ventral root (L7) and/or injection into the triceps surae (GS) muscle. 2. A direct application of BTA into the spinal cord led to a decrease of the early and the late response of RCs. 3. When the neurotoxin was injected into the GS muscle, the RC activity remained unaffected during the test period (33-46 h after application). 4. No effect appeared up to 10 h after an injection into the ventral root L7. 5. The RC-induced inhibition on IaINs, when tested in animals with local botulismus, remained intact during the test period. 6. From the present results it is suggested that on the spinal level the central action of botulinum toxin predominantly passes on the motoneurones.

1. Botulinum toxin type A was injected into gastrocnemius muscles of cats and 2 days later its action on the monosynaptic gastrocnemius reflex and on the recurrent inhibition was investigated. 2. In early local botulism, no significant change in the monosynaptic gastrocnemius reflex was observed. 3. The inhibition by antidromic stimulation of the monosynaptic gastrocnemius reflex was significantly reduced. 4. During the early phases of local botulism an action of botulinum toxin on parts of the soma membrane of the alpha-motoneuron is suggested.