Intradermal administration of ATP augments methacholine-induced cutaneous vasodilation but not sweating in young males and females

Am J Physiol Regul Integr Comp Physiol. 2015 Oct 15;309(8):R912-9. doi: 10.1152/ajpregu.00261.2015. Epub 2015 Aug 19.


Acetylcholine released from cholinergic nerves is a key neurotransmitter contributing to heat stress-induced cutaneous vasodilation and sweating. Given that sympathetic cholinergic nerves also release ATP, ATP may play an important role in modulating cholinergic cutaneous vasodilation and sweating. However, the pattern of response may differ between males and females given reports of sex-related differences in the peripheral mechanisms governing these heat loss responses. Cutaneous vascular conductance (CVC, laser-Doppler perfusion units/mean arterial pressure) and sweat rate (ventilated capsule) were evaluated in 17 young adults (8 males, 9 females) at four intradermal microdialysis skin sites continuously perfused with: 1) lactated Ringer (Control), 2) 0.3 mM ATP, 3) 3 mM ATP, or 4) 30 mM ATP. At all skin sites, methacholine was coadministered in a concentration-dependent manner (0.0125, 0.25, 5, 100, 2,000 mM, each for 25 min). In both males and females, CVC was elevated with the lone infusion of 30 mM ATP (both P < 0.05), but not with 0.3 and 3 mM ATP compared with control (all P >0.27). However, 0.3 mM ATP induced a greater increase in CVC compared with control in response to 100 mM methacholine infusion in males (P < 0.05). In females, 0.3 mM ATP infusion resulted in a lower concentration of methacholine required to elicit a half-maximal response (EC50) (P < 0.05). In both males and females, methacholine-induced sweating was unaffected by any concentration of ATP (all P > 0.44). We demonstrate that ATP enhances cholinergic cutaneous vasodilation albeit the pattern of response differs between males and females. Furthermore, we show that ATP does not modulate cholinergic sweating.

Keywords: muscarinic receptor; purinergic receptor; sudomotor activity; vasomotor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / administration & dosage
  • Adenosine Triphosphate / pharmacology*
  • Female
  • Humans
  • Injections, Intradermal
  • Male
  • Methacholine Chloride / administration & dosage
  • Methacholine Chloride / pharmacology*
  • Skin / blood supply*
  • Sweating / drug effects*
  • Urine / chemistry
  • Vasodilation / drug effects*
  • Young Adult


  • Methacholine Chloride
  • Adenosine Triphosphate