It's really going to depend on context. UK users have no problem with sites like delicious which have overseas TLDs.
If someone is searching for something overtly regional, then they are likely to opt for either regional triggers in the snippets they see, or alternatively a regional TLD. My personal opinion is that the text users see prior to clickthrough is the issue, rather than the domain name itself (but note that .co.uk involves seeing 'uk' prior to clickthrough).
I almost always advise a regional domain name if a campaign (you don't specify if this is SEO or advertising?) is regionally-targeted.
the text users see prior to clickthrough is the issue, rather than the domain name
I agree - domain extension is irrelevant as long as the language of the page is not foreign.
More importantly, though, the British tend to select Google's "pages from the UK" option when shopping, as it provides relevant local results that avoid problems with import taxes, shipping costs and incompatibile products from across the pond.
For information searches they will generally tolerate colonial mis-spellings of English.