WASHINGTON (AP) — Senate Republicans are reckoning with an insurgent's win in Alabama that poses clear threats to their own grip on power and the leadership of Majority Leader Mitch McConnell.

Nearly $10 million spent by a McConnell-backed super PAC couldn't save incumbent GOP Sen. Luther Strange, who had been endorsed by President Donald Trump as well. It came the same day that McConnell, short of votes, pulled the plug on the latest and possibly final GOP effort to repeal and replace "Obamacare."

Coming together, the events raised questions Wednesday about McConnell's leadership within the Senate and without, casting doubt on his reputation both as a seasoned political operator and a nearly unbeatable vote-counter on Capitol Hill.

"I'd hate to think about where we would be without Sen. McConnell's efforts. But I think we'll learn from it, and we'll adjust," McConnell's No. 2, Sen. John Cornyn of Texas, said of the victory of rabble-rousing former jurist Roy Moore, known for hanging the Ten Commandments in his courtroom in defiance of federal court orders. "We're all listening and watching very closely and trying to understand the message that's being sent."

To some conservative campaign operatives, there was little question about that message.

"Alabama was a rejection of Mitch McConnell and the entire Republican establishment that he represents," said Andy Surabian, senior adviser to the pro-Trump group Great America Alliance, which spent more than $150,000 on Moore's behalf.

"Everyone is going to be under the microscope. That doesn't mean everyone is going to have a serious primary challenger," he said. "But if you think you're going to be able to take a cheap shot at the president to score a few political points in the mainstream media, you have another thing coming."

McConnell allies strongly disputed claims that he was a drag on Strange, arguing that despite low approval ratings that come with being a party leader in Congress, there was scant real evidence that opposition to the Kentucky Republican was a motivating factor for voters in a race where local issues, including the former governor's corruption scandal, played a major role. But one Republican operative working on 2018 Senate races, who requested anonymity to discuss internal GOP dynamics, said the party is increasingly worried about the impact of McConnell's unpopularity among GOP voters on establishment primary candidates, particularly after another health care failure.

McConnell did get a vote of confidence, of sorts, from Trump, who told reporters asking whether he had confidence in the majority leader: "I do have confidence in him, yes. I do have confidence. But it's really not up to me, it's up to the Senate, but I do have confidence in him. I will say they used him in the race, and I was very honored by the way I was treated in the race, but they used him in the race."

Republican senators, too, worried about the political fallout from Strange's loss heading into an election cycle where they will be defending a slim 52-48 majority. Although few GOP incumbents are seen as truly vulnerable, others could attract troublesome primary challenges like those already looming for Republican Sens. Dean Heller of Nevada, Jeff Flake of Arizona and potentially Roger Wicker of Mississippi.

"This is going to be interpreted by the so-called anti-establishment forces as a victory they can build on and I suspect they'll be out recruiting candidates to try and primary many of our incumbent senators," said Sen. John Thune of South Dakota.

Already this week, rounding out McConnell's woes, Tennessee GOP Sen. Bob Corker announced plans to retire rather than seek re-election next year in face of certain primary opposition.

Strange's loss in Alabama was the first for McConnell's well-funded and highly professional operation since he made the decision to get involved in Senate primaries five years ago, after a spate of oddball conservatives got into general elections in the 2010 and 2012 cycles and went on to lose to Democrats. The Senate Leadership Fund, led by former McConnell Chief of Staff Steve Law, invested heavily in the race to try to keep Strange in the Senate.

The group's failure could send hesitant GOP incumbents the message that for all his efforts, McConnell might not be able to save them from a roiled and angry electorate.

In a memo assessing the election, Law ticked off several conclusions that bode ill for the GOP in the election cycle ahead, including that "the Republican Congress has replaced President Obama as the bogeyman for conservative GOP primary voters" and "the Obamacare repeal fiasco is political poison."

Also problematic for McConnell may be Moore's arrival in the Senate, presuming he beats the Democrat in December's general election. McConnell is already struggling to hold together his 52-vote majority, as the failure on health care shows, and will now have an additional squeaky wheel to deal with rather than the reliable vote Strange offered.

An aide to McConnell said the majority leader spoke with Moore on Wednesday.

Moore declared his opposition to McConnell throughout the campaign, but interviewed Wednesday on Fox News Channel he said he would support the majority leader when their goals align.

"As long as he stands for a conservative agenda and what we promised the people as Republicans, I'll work with anyone," Moore said.

That apparently doesn't include health care, though. While Trump insisted repeatedly Wednesday that the latest GOP health care plan would eventually succeed, Moore decried it as "socialized medicine at best."

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Associated Press writer Tom Beaumont in Des Moines, Iowa, contributed to this report.