The effects of deleting the mouse neurotensin receptor NTR1 on central and peripheral responses to neurotensin

ABSTRACT Mice deficient in the neurotensin (NT)-1 receptor (NTR1) were developed to characterize the NT receptor subtypes that mediate various in vivo responses to NT. F2 generation (C57BL6/ Sv129J) NTR1 knockout (Ϫ/Ϫ) mice were viable, and showed normal growth and overt behavior. The Ϫ/Ϫ mice lacked detectable NTR1 radioligand binding in brain, whereas NTR2 receptor binding density appeared normal compared with wildtype (ϩ/ϩ) mice. The gene deletion also resulted in the loss of NTR1 expression as determined by reverse transcription-polymerase chain reaction and in situ hybridization. Intracerebroventricular injection of NT (1 g) to ϩ/ϩ mice caused a robust hypothermic response (5-6°C) and a significant increase in hot-plate latency. These effects were absent in the Ϫ/Ϫ mice. Similar results were obtained with i.p. injections of the brainpenetrant NT analog NMe-Arg-Lys-Pro-Trp-Tle-Leu (NT-2, 1 mg/kg i.p.). NT-2 administration also impaired rotarod performance in wild-type mice, but had no effect on motor coordination in knockout mice. In vitro, NT and NT-2 at 30 nM caused predominantly contraction and relaxation in isolated distal colon and proximal ileum, respectively, from ϩ/ϩ mice, but no responses were observed with tissues from Ϫ/Ϫ mice. A similar loss of the contractile effects of NT was observed in the isolated stomach fundus from the knockout mice. In vivo, NT-2 administration reduced colonic propulsion substantially in wild-type mice. In contrast, NT-2 had no effect in NTR1 null mice, whereas the hypomotility effect of clonidine was intact. These data indicate that NTR1 mediates several of the central and peripheral effects of NT

Governance for a “socialised economy”. A case study in preventive health and work integration

This work is motivated by the question of how organisational governance can address the needs of vulnerable groups. This paper offers a conceptual reflection on how the production of complex health-related services, such as aspects of preventive psychiatric illnesses, can be governed to the benefit of users and communities society more broadly. The analysis is applied to a consortium of twenty-two social enterprises (SEs), with worker membership, located in Italy. The governance model adopted by the consortium is of particular interest since it pioneered solutions based on the combination of preventive health and work integration services. The case, specifically, allows to illustrate and analyse interdependencies amongst multiple publics, and how these are reflected by the governance model. Specifically, the findings suggest that central to the success of the model in meeting such challenges are: a) the integration of different but complementary organisations and competencies, including health, social, and production competences; b) a mix of interdependent governance solutions, each activating different types of publics and social capital; c) membership, through which workers partake in decision-making; d) formal fiduciary duties between vulnerable publics and members complemented by bonding and bridging social relations; e) the integration of community assets as inputs into the process, and the creation of societal outputs in terms of employment, social integration and cohesion