MIT₁, a black mamba toxin with a new and highly potent activity on intestinal contraction

Abstract

Mamba intestinal toxin (MIT 1 ) isolated from Dendroaspis polylepis venom is a 81 amino acid polypeptide crosslinked by five disulphide bridges. MIT 1 has a very potent action on guinea-pig intestinal contractility. MIT 1 (1 nM) potently contracts longitudinal ileal muscle and distal colon, and this contraction is equivalent to that of 40 mM K + . Conversely MIT 1 relaxes proximal colon again as potently as 40 mM K + . The MIT 1 -induced effects are antagonised by tetrodotoxin (1 W WM) in proximal and distal colon but not in longitudinal ileum. The MIT 1 -induced relaxation of the proximal colon is reversibly inhibited by the NO synthase inhibitor L-NAME (200 W WM). 125 Ilabelled MIT 1 binds with a very high affinity to both ileum and brain membranes (K d = 1.3 pM and 0.9 pM, and B max = 30 fmol/ mg and 26 fmol/mg, respectively). MIT 1 is a very highly selective toxin for a receptor present both in the CNS and in the smooth muscle and which might be an as yet unidentified K + channel.z 1999 Federation of European Biochemical Societies.

Characterization of Endocrine Gland-derived Vascular Endothelial Growth Factor Signaling in Adrenal Cortex Capillary Endothelial Cells

“…Both VPRA/EG-VEGF (20,23) and the "Bv8" proteins have been shown to induce contractions of ileum and distal colon and relaxation of proximal colon (21,23). Notably, N -nitro-L-arginine methyl ester reversibly inhibited VPRA-induced relaxation of proximal colon, indicating that NO synthesis is required for such effect (20). Interestingly, Li et al (23) concluded, on the basis of pharmacological evidence, that the contractility-enhancing effects on guinea pig ileum of "prokineticin-1" (identical to EG-VEGF) were mediated by a GPCR.…”

“…The first of such molecules, venom protein A (VPRA) (19), known also as "MIT-1" (20), was purified from the venom of black mamba snake (Dendroaspis polylepis polylepis) as a nontoxic component. EG-VEGF is most likely the human orthologue of VPRA, and the two proteins display 80% homology (18).…”

Abnormal development of the olfactory bulb and reproductive system in mice lacking prokineticin receptor PKR2

“…Moreover, PKRs also couple to Gqi and Gs proteins, indicating that PKRs activate multiple intracellular signal-transduction pathways (6,7). Activation of PKRs influences several physiological events in the CNS and peripheral tissues (8), including intestinal contraction (9), hyperalgesia (10,11), spermatogenesis (12), neuronal survival (13), circadian rhythm (14,15), angiogenesis (16)(17)(18), ingestive behavior (19), and hematopoiesis (20). Recently, Ng et al (21) reported the generation of knockout mice lacking Pk2 (Pk2 Ϫ/Ϫ mice).…”

Discovery of an MIT-like atracotoxin family: Spider venom peptides that share sequence homology but not pharmacological properties with AVIT family proteins

“…3. This includes MIT1 from the venom of the black mamba snake Dendroaspis p. polylepis [2,39], Bv8 (Bombina variegata 8 kDa protein; [32]) and its orthologs Bm8a-f (B. maxima 8 kDa protein; [4,21]) from the skin secretions of toads from Bombina spp., and the recently identified prokineticin 1 (PK1; also known as endocrine-gland vascular endothelial growth factor or EG-VEGF) and prokineticin 2 (PK2) peptides [27]. These are all 77-94 residue peptides, containing 10 cysteines with conserved spacing, whose N-terminal four residues, 'AVIT', are all identical (Fig.…”