Ask Daphne! Have I orphaned my sequel?

A classic lone shoe movie poster for MD, who writes:

Since I couldn’t drum up agent interest with my first book, I have written a sequel (how dumb is that?). I’m testing with new critters to make sure it’s standalone, but should I mention that this second book is just that: a second book in a series. I have a few more ideas to continue this series, so I’m sure it could be at least three or more. How do I pitch a second book? Also, since agents didn’t want it, I’ve sent it directly to publishers and gotten more positive responses. Will a publisher acceptance of Book 1 kill any possibility for Book 2 getting an agent? Of course, the publishers are small, therefore of no interest to agents. Should I withdraw Book 1 from the small publishers and hold out for a agent deal?

Lots of questions in one! Let’s see if we can’t make some order from chaos.
In sending your book out to agents for consideration, should you mention that it’s the second book in a series? I say no. Granted, you have to be completely sure that it does work as a standalone, but there’s a possibility that the reasons the first book was rejected do not apply to the second book. Maybe you’re grown as a writer, and fixed newbie mistakes. As long as book 2 holds up as a standalone, don’t let the weight of book 1 hold it down. if you must, say only that you can envision a number of other stories in this world that could be explored in future books.
Then, you’re saying that since agents didn’t want Book 1, you sent it to small publishers, who are expressing interest. Should you withdraw it from them on the hopes of an agent being interested in Book 2? Again, I say no. Even a request for a full manuscript isn’t a guarantee, and as your own best advocate, you have to explore every possibility if you want your book to see its way to market. See what happens with the small publishers!
If you’re lucky enough to land a publishing deal on your own with a small press (or with anyone, really), and you already have book two out and about, then you could go back to agents who are considering partials or fulls of book 2 and tell them the good news. Of course, many of them may want to see how book 1 does on the marketplace, and how your publisher is going to position it, but they might be able to help you land either a better deal for book 2, or a new home.
On a completely different note, have you tried writing a different book altogether? Consider pitching your career to agents with a novel that doesn’t require any further reading, and is, in fact, a standalone. See how that goes.
Good luck!