In the wake of three incursions by NATO helicopters into Pakistani air space in less than a week, protests broke out Friday in Pakistan, with some leaders calling NATO's strikes on militant strongholds "an act of war."

Militants responded Friday by attacking 27 NATO fuel trucks north of Karachi, and two drivers were burned alive in a separate incident. The attacks were seen as retaliation for NATO's latest cross-border helicopter strike, which mistakenly killed three Pakistani border police earlier this week.

Khurshid Ahmed, a member of the opposition party in Pakistan, demanded that the NATO strikes stop.

"We regard it as an act of war, and we have demanded that Pakistan government must take immediate steps," he said, "both stopping supplies to NATO and, No. 2, if our borders are violated we should strike back."

Pakistani Prime Minister Yousuf Raza Gilani also hinted at the prospect of further retaliation.

"We have other options, too," Gilani said after meeting with CIA chief Leon Panetta, who flew to Islamabad Wednesday to discuss an unfolding terror plot in Europe, one with roots in Pakistan's tribal areas.

The Pakistani government has closed the main supply route into Afghanistan at the Torkham border in the Khyber pass, leaving 150 NATO supply trucks stuck at the border. Some top Pakistani officials are asking whether the U.S. and Pakistan are allies or enemies.

"People ask questions: If you are being attacked, are you fighting a war or are you in a war together?" Rehman Malik, Pakistan's interior minister, said.

Protests broke out in Pakistani cities Friday, with angry mobs blaming the U.S. and NATO for Pakistan's problems. One protest banner carried the message, "Who is responsible for the destruction of Pakistan?"

Even some local truck drivers employed by NATO think Pakistan should stop the supply route.

"The government should stop all these supplies," Fazal Khan, one driver for NATO, said. "It should stop the supplies for two, three months, so that they (NATO forces) feel the pinch and they stop the massacre of Muslims."

Pakistani officials have played a double game in recent years, criticizing U.S. attacks in its tribal areas publicly while encouraging the drone strikes on Al Qaeda leaders in private. According the the recent Bob Woodward book, "Obama's Wars," Pakistan President Asif Zardari told then CIA head Michael Hayden to step up the drone strikes against Al Qaeda in Pakistan.

"Collateral damage worries you Americans. It does not worry me," Zardari is quoted as saying.

U.S. officials downplayed the border closure Friday.

"It is inconceivable to me that the closing of the routes ... would continue more than a short period of time," said Richard Holbrooke, the U.S. special envoy to Pakistan and Afghanistan.

U.S. officials are pretty confident the border crossing will be opened shortly because the Pakistanis make so much money off the passage of goods that they will be harming themselves as much as they are harming the U.S. and NATO if it remains closed.

Fox News' Jennifer Griffin and Justin Fishel contributed to this report.