Boris Johnson’s premiership has been dealt an extraordinary blow after his brother, Jo Johnson, announced he was quitting the cabinet, citing an “unresolvable tension” between his family loyalty and the national interest.

The dramatic move by the younger Johnson, who had only recently returned to government, sent shockwaves through the Conservative party and appeared to severely rattle the prime minister as he visited a police training academy.

The speech by the prime minister in West Yorkshire was to have marked the start of a Conservative general election campaign – a schedule scuppered by Labour overnight. Johnson pledged he would rather “die in a ditch” than bow to the demands of the no-deal bill passed by the House of Commons and request a Brexit extension.

However, Downing Street appeared to be increasingly losing control of the timetable, with Johnson unable to articulate how he would react should Labour fail to back an election again on Monday, in a rambling and occasionally incoherent speech, delivered almost an hour late.

Asked about the departure of his brother, the prime minister said: “Look, people disagree about the EU. The way to unite the country, I’m afraid, is to get this thing done. That is the reality.”

Jo Johnson had only recently returned to government as a business minister with a brief that saw him attend his brother’s cabinet – after quitting a different frontbench role earlier this year in order to back a second referendum.

His return had raised eyebrows in Westminster after his brother was confirmed as prime minister in July, but he suggested he could no longer reconcile his differences with his brother over Brexit – just days after 21 Conservative MPs lost the whip for backing moves to stop no deal.

In a statement on Twitter, Johnson said it had been an honour to represent Orpington for nine years and to serve as a minister under three PMs.

“In recent weeks I’ve been torn between family loyalty and the national interest – it’s an unresolvable tension and time for others to take on my roles as MP & minister. #overandout,” he tweeted.

Johnson’s resignation looks set to become a major attack line for Labour. “Boris Johnson poses such a threat that even his own brother doesn’t trust him,” the party’s shadow education secretary Angela Rayner said.

His departure also came amid a number of resignations from Conservative MPs who cited the divisions in the party. Caroline Spelman, the former party chair who rebelled against the government to back the bill on Wednesday, said she would leave parliament because “I can’t be pro no-deal when I’ve seen the predictions about what will happen to jobs.”

Nick Hurd, the Northern Ireland minister, also said he would not stand again, saying politics “is now dominated by the ongoing division over Brexit.”

It is understood Johnson told the prime minister of his decision to quit in a tense phone call on Wednesday night but Downing Street acknowledged the difficulties of the familial dilemma in a statement, thanking Johnson for his time as a minister.

“The prime minister would like to thank Jo Johnson for his service. He has been a brilliant, talented minister and a fantastic MP,” a No 10 spokesman said.

“The PM, as both a politician and brother, understands this will not have been an easy matter for Jo. The constituents of Orpington could not have asked for a better representative.”

Speaking to the Sun, Jo Johnson said his argument with his brother was over Brexit alone. “What is so clearly in the national interest is everything the government is doing in its strong, one nation domestic policy agenda: more police on the streets, more doctors and nurses in our hospitals, a welcoming face to scientists and international students,” he said.

“That’s exactly what a Conservative prime minister should be doing and what Boris does so well.”

Johnson’s spokeswoman, when asked if the prime minister believed he was acting in the national interest, said: “The prime minister is working incredibly hard to deliver what the people voted for.” Asked again if that was in the national interest, the spokeswoman said: “Yes.”

A number of MPs who lost the Conservative whip on Tuesday night praised Jo Johnson’s move, citing his bravery. The former justice secretary David Gauke said: “Lots of MPs have had to wrestle with conflicting loyalties in recent weeks. None more so than Jo. This is a big loss to parliament, the government and the Conservative party.”

Margot James, the former digital minister, said to Johnson: “If I thought my decision had been difficult it was nothing compared to yours. I am utterly humbled by your action and statement today.”

Nick Boles, the former Conservative MP, said Jo Johnson’s departure showed the lengths his brother would go. “Boris Johnson is willing to sacrifice anyone and anything on the altar of his ego and ambition. His lust for power consumes everyone who stands in his way,” he tweeted.

The move comes amid mounting tension between Downing Street and MPs over the treatment of Conservatives who lost the whip. Damian Green, the former deputy prime minister who chairs the One Nation group of moderate Conservatives, wrote to Boris Johnson overnight on behalf of the group asking him to reconsider removing the whip.

“I’m afraid it does look as though somebody has decided that the moderate, progressive wing of the Conservative party is not wanted on the voyage,’” Green told the BBC on Thursday.

The Guardian understands several cabinet ministers, including Michael Gove, Amber Rudd and Matt Hancock, asked the prime minister at a cabinet meeting on Wednesday if there was a possibility of reprieve for their former colleagues but were told that was impossible.

The cabinet ministers’ intervention, first reported by the Sun, came as other Conservatives reiterated demands that Brexiter MPs receive the same treatment should they vote down any new withdrawal agreement, including from former defence minister Tobias Ellwood.

Johnson will seek to trigger an election again on Monday, daring Labour not to back the motion after the no-deal bill has been made law, but it is unclear how the prime minister will proceed beyond that – given he has sworn not to abide by the law that will say he must ask the EU to extend the Brexit deadline.

The leader of the House of Commons, Jacob Rees-Mogg, said the government would seek to bring the same motion back and that parliament would not be prorogued until the bill had received royal assent.

Downing Street will resubmit the same motion that needs a two-thirds majority under the Fixed-term Parliaments Act. Should the motion pass, parliament is expected to be prorogued on Monday but should it fail, Johnson has the option of attempting another route and keeping parliament going until Thursday – the deadline for prorogation.

The House of Commons Speaker, John Bercow, has previously objected to the same motion being put forward twice when Theresa May attempted to submit her Brexit deal on multiple occasions, but No 10 believes it will be permitted because of the no-deal bill receiving royal assent, a material change of circumstances.

Should the plan fail, Johnson will be faced with the difficult dilemma of trying to force an election using a different route that requires only a simple majority – either a one-line bill to amend the Fixed-term Parliament Act or calling a no-confidence vote in his own government.

A Downing Street source reiterated that the prime minister would under no circumstances go to Brussels to request an extension beyond the October deadline.

“It will never, ever, ever happen, we will never do it and so eventually we will get an election,” the source said. “Watch Labour’s polling drop off a cliff when the country sees what they are trying to do.”